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Review Open Access

IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review)

  • Authors:
    • Hao Zhu
    • Hao Wang
    • Xia Li
    • Weisong Zhang
    • Yihao Wang
    • Qingze Tan
    • Dongxu Ying
    • Zhan Shi
    • Jianxiang Song
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, Yancheng, Jiangsu 224000, P.R. China, Department of General Medicine, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, Yancheng, Jiangsu 224000, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 81
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    Published online on: February 3, 2026
       https://doi.org/10.3892/ijmm.2026.5752
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Abstract

Metabolic reprogramming is a hallmark feature of malignant tumors. These metabolic pathways are regulated in a cell‑autonomous manner by oncogenic signaling and transcriptional networks, and tracking their metabolic reprogramming is frequently used in the diagnosis, detection and treatment of cancer. There are currently promising therapeutic prospects for a variety of types targeting fixed core metabolic pathways in tumor metabolic reprogramming. Among these, inosine monophosphate (IMP) is an essential intermediate in purine nucleotide synthesis that demonstrates significant target potential. Nevertheless, further research is needed to elucidate the regulatory networks that control IMP metabolism in tumor cells. This review combines the latest insights into IMP metabolism into an interesting conceptual framework. This includes the supply of IMP precursor substrates (reprogramming of glucose metabolism, serine/one‑carbon metabolism, glutamine and mitochondrial metabolism), the dynamic regulation of important enzymes [phosphoribosyl pyrophosphate synthetase, phosphoribosyl pyrophosphate amidotransferase, IMP dehydrogenase (IMPDH)], purinosomes and signaling pathways (RAS‑ERK, PI3K/AKT‑mTORC1 and Hippo‑YAP) that ultimately regulate IMP synthesis in tumor cells. Additionally, it focused on downstream associations between IMPDH and the immune microenvironment, offering a fresh perspective for current research on tumor therapy targeting IMP metabolism.
View Figures

Figure 1

The synthesis process of purine
nucleotides in the human body. The organism synthesizes the
required purine nucleotides by taking in energy and raw materials
from the external environment. PRPP, phosphoribosyl diphosphate;
PPAT, phosphoribosyl pyrophosphate amidotransferase; GART,
glycinamide ribonucleotide transformylase; PFAS,
phosphoribosylformylglycinamidine synthase; PAICS,
phosphoribosylaminoimidazole succinocarboxamide synthetase; ADSL,
adenylosuccinate lyase; ATIC, 5-aminoimidazole-4-carboxamide
ribonucleotide formyltransferase/IMP cyclohydrolase; ADSS,
adenylosuccinate synthetase; IMPDH, inosine monophosphate
dehydrogenase; GMPS, guanosine monophosphate synthetase; APRT,
adenine phosphoribosyltransferase; HPRT, hypoxanthine-guanine
phosphoribosyltransferase.

Figure 2

During de novo IMP synthesis,
multiple metabolic pathways precisely converge to provide essential
carbon skeletons and nitrogen sources. The figure illustrates key
reactions in central metabolism, including how glucose, glutamine,
serine/glycine, one-carbon and mitochondrial metabolism supply
substrates for de novo IMP synthesis. IMP, inosine
monophosphate; HK, hexokinase; G6P, glucose-6-phosphate; GPI,
glucose-6-phosphate isomerase; F6P, fructose-6-phosphate; PFK1,
phosphofructokinase 1; F1,6BP, fructose-1,6-bisphosphoglycerate;
aldolase, fructose-bisphosphate aldolase; DHAP, dihydroxyacetone
phosphate; TPI1, triosephosphate isomerase 1; GAPDH,
glyceraldehyde-3-phosphate dehydrogenase; 1,3BPG,
1,3-bisphosphoglycerate; PGK, phosphoglycerate kinase; 3-PG,
3-phosphoglycerate; PGAM, phosphoglycerate mutase; 2-PG,
2-phosphoglycerate; PEP, phosphoenolpyruvate; PK, pyruvate kinase;
LDH, lactate dehydrogenase; PPP, pentose phosphate pathway; G6PD,
glucose-6-phosphate dehydrogenase; Non-oxidative PPP, non-oxidative
pentose phosphate pathway; R5P, ribose-5-phosphate; PRPS,
phosphoribosyl pyrophosphate synthetase; PRPP,
5-phosphoribosyl-1-pyrophosphate; GLU, glutamate; PHGDH,
phosphoglycerate dehydrogenase; PSAT1, phosphoserine
aminotransferase 1; PSPH, phosphoserine phosphatase; PDH, pyruvate
dehydrogenase; PC, pyruvate carboxylase; AcCoA, acetyl-CoA; TCA
cycle, tricarboxylic acid cycle; CS, citrate synthase; CIT,
citrate; IDH2/3, isocitrate dehydrogenase 2/3; αKGDH, α-KG
dehydrogenase; SUC, succinate; SDH, succinate dehydrogenase; FUM,
fumarate; FH, fumarate hydratase; MAL, malate; MDH2, malate
dehydrogenase 2; OAA, oxaloacetate; GOT2, glutamate oxaloacetate
transaminase 2; ASP, aspartate; Gly, glycine; mTHF,
5,10-methylenetetrahydrofolate; fTHF, 10-formyltetrahydrofolate;
THF, tetrahydrofolate; SHMT1/2, serine hydroxymethyltransferase
1/2; FOR, formate; Mt 1C cycle, mitochondrial one-carbon cycle;
MTHFD1L, methylenetetrahydrofolate dehydrogenase 1-like; GLN,
glutamine; NH4+, ammonium; GLS, glutaminase;
GS, glutamine synthetase; ALA, alanine; PYR, pyruvate; GDH,
glutamate dehydrogenase; GPT2, alanine aminotransferase 2.

Figure 3

The de novo synthesis and
salvage pathways for IMP starting from R5P. In cancer cells, the
Warburg effect enhances glycolytic flux, which in turn fuels the
PPP through both oxidative and non-oxidative branches, thereby
increasing the availability of R5P for purine biosynthesis. Under
conditions of elevated metabolic demand, purine biosynthetic
enzymes assemble into dynamic purinosomes to promote efficient
metabolic flux toward IMP production. The purinosome core
components (PPAT, GART and PFAS) interact with PAICS, ADSL and
ATIC, which also dynamically associate with each other. PPP,
pentose phosphate pathway; ox, oxidative; non-ox, non-oxidative;
R5P, ribose-5-phosphate; PRPS, phosphoribosyl pyrophosphate
synthetase; PRPP, 5-phosphoribosyl-1-pyrophosphate; Gln, glutamine;
Gly, glycine; PRAT, phosphoribosyl pyrophosphate amidotransferase;
5-PRA, 5-phosphoribosylamine; GARS, glycinamide ribonucleotide
synthetase; GAR, glycinamide ribonucleotide; GART, glycinamide
ribonucleotide transformylase; fTHF, 10-formyltetrahydrofolate;
FGAR, formylglycinamide ribonucleotide; PFAS,
phosphoribosylformylglycinamidine synthase; FGAM,
formylglycinamidine ribonucleotide; AIRS, aminoimidazole
ribonucleotide synthetase; AIR, aminoimidazole ribonucleotide;
PAICS, phosphoribosylaminoimidazole succinocarboxamide synthetase;
CAIR, carboxyaminoimidazole ribonucleotide; Asp, aspartate; SAICAR,
succinylaminoimidazolecarboxamide ribonucleotide; ADSL,
adenylosuccinate lyase; AICAR, 5-aminoimidazole-4-carboxamide
ribonucleotide; FAICAR, 5-formamidoimidazole-4-carboxamide
ribonucleotide; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide
formyltransferase/IMP cyclohydrolase; HPRT, hypoxanthine-guanine
phosphoribosyltransferase; IMP, inosine monophosphate; Hsp90, heat
shock protein 90.

Figure 4

Regulation of de novo IMP
synthesis by cellular signaling networks. (A) Under growth factor
stimulation, mTORC1 is activated downstream of the PI3K/Akt
pathway, stimulating SLC4A7 mRNA translation via s6k-dependent
eIF4B phosphorylation. This increases cellular bicarbonate
abundance, thereby promoting IMP resynthesis. Downstream of mTORC1,
transcription factor SREBP1 stimulates the oxidative PPP, enhancing
de novo IMP synthesis by increasing PRPP availability; Akt
activates the non-oxidative PPP via TKT phosphorylation, promoting
PRPP-dependent IMP synthesis. Furthermore, mTORC1 activates MYC,
which upregulates de novo purine synthase expression,
thereby promoting de novo IMP synthesis. Furthermore, mTORC1
activation enhances ATF4 expression, promoting serine/glycine
synthesis and fTHF production to increase IMP de novo
synthesis. Crucially, PTEN antagonizes PI3K/AKT activation, acting
as a counterbalance. (B) Under growth factor influence, ERK
phosphorylates PFAS, promoting IMP de novo synthesis.
Concurrently, MYC, a downstream transcription factor of RAS-ERK,
regulates gene expression involved in de novo IMP synthesis.
(C) Under growth factor stimulation, MST1/LAST1 activates YAP,
upregulating glutamine synthase GLUL expression to enhance
glutamine synthesis and thereby promote de novo IMP
synthesis. YAP directly activates TRIO to regulate the Rac1/RhoA
switch and STAT3, forming the YAP-TRIO-RhoGTPase-STAT3 signaling
network that governs cell migration and invasion. PPP, pentose
phosphate pathway; IMP, inosine monophosphate; PTEN, phosphatase
and tensin homolog; PI3K, phosphoinositide 3-kinase; AKT, protein
kinase B; mTORC1, mechanistic target of rapamycin complex 1; ATF4,
activating transcription factor 4; SREBP1, sterol regulatory
element-binding protein 1; PRPP, 5-phosphoribosyl-1-pyrophosphate;
IMP, inosine monophosphate; MYC, MYC proto-oncogene, bHLH
transcription factor; S6K, ribosomal protein S6 kinase; eIF4B,
eukaryotic translation initiation factor 4B; TKT, transketolase;
SLC4A7, solute carrier family 4 member 7; HCO3-, bicarbonate; mTHF,
5,10-methylenetetrahydrofolate; THF, tetrahydrofolate; RAS, rat
sarcoma; MEK, mitogen-activated protein kinase kinase; ERK,
extracellular signal-regulated kinase; PFAS,
phosphoribosylformylglycinamidine synthase; RP1A, ribose phosphate
isomerase A; D5P, D-ribose-5-phosphate; LATS1, large tumor
suppressor kinase 1; YAP, yes-associated protein; GLUT, glucose
transporter; TRIO, triple functional domain protein; RhoGTPase, Rho
family GTPase; STAT3, signal transducer and activator of
transcription 3.
View References

1 

Tran DH, Kim D, Kesavan R, Brown H, Dey T, Soflaee MH, Vu HS, Tasdogan A, Guo J, Bezwada D, et al: De novo and salvage purine synthesis pathways across tissues and tumors. Cell. 187:3602–3618.e20. 2024. View Article : Google Scholar : PubMed/NCBI

2 

Zarrella S, Miranda MR, Covelli V, Restivo I, Novi S, Pepe G, Tesoriere L, Rodriquez M, Bertamino A, Campiglia P, et al: Endoplasmic reticulum stress and its role in metabolic reprogramming of cancer. Metabolites. 15:2212025. View Article : Google Scholar : PubMed/NCBI

3 

Villa E, Ali ES, Sahu U and Ben-Sahra I: Cancer cells tune the signaling pathways to empower de novo synthesis of nucleotides. Cancers (Basel). 11:6882019. View Article : Google Scholar : PubMed/NCBI

4 

Murray AW: The biological significance of purine salvage. Annu Rev Biochem. 40:811–826. 1971. View Article : Google Scholar : PubMed/NCBI

5 

Pareek V, Pedley AM and Benkovic SJ: Human de novo purine biosynthesis. Crit Rev Biochem Mol Biol. 56:1–16. 2021. View Article : Google Scholar

6 

Camici M, Garcia-Gil M, Pesi R, Allegrini S and Tozzi MG: Purine-metabolising enzymes and apoptosis in cancer. Cancers (Basel). 11:13542019. View Article : Google Scholar : PubMed/NCBI

7 

He J, Zou LN, Pareek V and Benkovic SJ: Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling. J Biol Chem. 298:1018532022. View Article : Google Scholar : PubMed/NCBI

8 

Pedley AM and Benkovic SJ: A new view into the regulation of purine metabolism: The purinosome. Trends Biochem Sci. 42:141–154. 2017. View Article : Google Scholar

9 

Lu M, Wu Y, Xia M and Zhang Y: The role of metabolic reprogramming in liver cancer and its clinical perspectives. Front Oncol. 14:14541612024. View Article : Google Scholar : PubMed/NCBI

10 

Hon KW, Zainal Abidin SA, Othman I and Naidu R: The crosstalk between signaling pathways and cancer metabolism in colorectal cancer. Front Pharmacol. 12:7688612021. View Article : Google Scholar : PubMed/NCBI

11 

Pandey S, Singh R, Habib N, Tripathi RM, Kushwaha R and Mahdi AA: Regulation of hypoxia dependent reprogramming of cancer metabolism: Role of HIF-1 and its potential therapeutic implications in leukemia. Asian Pac J Cancer Prev. 25:1121–1134. 2024. View Article : Google Scholar : PubMed/NCBI

12 

Shi JZ, Zhu YJ, Zhang MJ, Yan Y, Zhao LL, Zhang HD, Liu Y, Wu WH, Cheng Z, Qiu CG, et al: Hypoxanthine promotes pulmonary vascular remodeling and adenosine deaminase is a therapeutic target for pulmonary hypertension. JACC Basic Transl Sci. 10:1012732025. View Article : Google Scholar : PubMed/NCBI

13 

Cuny GD, Suebsuwong C and Ray SS: Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: A patent and scientific literature review (2002-2016). Expert Opin Ther Pat. 27:677–690. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Cholewiński G, Iwaszkiewicz-Grześ D, Prejs M, Głowacka A and Dzierzbicka K: Synthesis of the inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors. J Enzyme Inhib Med Chem. 30:550–563. 2015. View Article : Google Scholar

15 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

16 

Weinhouse S: The Warburg hypothesis fifty years later. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 87:115–126. 1976. View Article : Google Scholar : PubMed/NCBI

17 

Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A and Saavedra E: Energy metabolism in tumor cells. FEBS J. 274:1393–418. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Moreno-Sánchez R, Rodríguez-Enríquez S, Saavedra E, Marín-Hernández A and Gallardo-Pérez JC: The bioenergetics of cancer: Is glycolysis the main ATP supplier in all tumor cells? Biofactors. 35:209–225. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Jing Z, Liu Q, He X, Jia Z, Xu Z, Yang B and Liu P: NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J Exp Clin Cancer Res. 41:1982022. View Article : Google Scholar : PubMed/NCBI

21 

Fang J, Luo S and Lu Z: HK2: Gatekeeping microglial activity by tuning glucose metabolism and mitochondrial functions. Mol Cell. 83:829–831. 2023. View Article : Google Scholar : PubMed/NCBI

22 

Fantin VR, St-Pierre J and Leder P: Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 9:425–434. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL and Cantley LC: The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 452:230–233. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Christofk HR, Vander Heiden MG, Wu N, Asara JM and Cantley LC: Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 452:181–186. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Patra KC and Hay N: The pentose phosphate pathway and cancer. Trends Biochem Sci. 39:347–354. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Riganti C, Gazzano E, Polimeni M, Aldieri E and Ghigo D: The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate. Free Radical Biol Med. 53:421–436. 2012. View Article : Google Scholar

27 

TeSlaa T, Ralser M, Fan J and Rabinowitz JD: The pentose phosphate pathway in health and disease. Nat Metab. 5:1275–1289. 2023. View Article : Google Scholar : PubMed/NCBI

28 

Wang X, Yang K, Xie Q, Wu Q, Mack SC, Shi Y, Kim LJY, Prager BC, Flavahan WA, Liu X, et al: Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nat Neurosci. 20:661–673. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Manganelli G, Masullo U, Passarelli S and Filosa S: Glucose-6-phosphate dehydrogenase deficiency: Disadvantages and possible benefits. Cardiovasc Hematol Disord Drug Targets. 13:73–82. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Fan TWM, Bruntz RC, Yang Y, Song H, Chernyavskaya Y, Deng P, Zhang Y, Shah PP, Beverly LJ, Qi Z, et al: De novo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues. J Biol Chem. 294:13464–13477. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Wu D, Zhang K, Khan FA, Pandupuspitasari NS, Guan K, Sun F and Huang C: A comprehensive review on signaling attributes of serine and serine metabolism in health and disease. Int J Biol Macromol. 260:1296072024. View Article : Google Scholar : PubMed/NCBI

32 

Shunxi W, Xiaoxue Y, Guanbin S, Li Y, Junyu J and Wanqian L: Serine metabolic reprogramming in tumorigenesis, tumor immunity, and clinical treatment. Adv Nutr. 14:1050–1066. 2023. View Article : Google Scholar : PubMed/NCBI

33 

Geeraerts SL, Heylen E, De Keersmaecker K and Kampen KR: The ins and outs of serine and glycine metabolism in cancer. Nat Metab. 3:131–141. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Tibbetts AS and Appling DR: Compartmentalization of Mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr. 30:57–81. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Huo FC, Xie M, Zhu ZM, Zheng JN and Pei DS: SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT. Genomics. 114:1104242022. View Article : Google Scholar : PubMed/NCBI

36 

Hennequart M, Labuschagne CF, Tajan M, Pilley SE, Cheung EC, Legrave NM, Driscoll PC and Vousden KH: The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells. Nat Commun. 12:61762021. View Article : Google Scholar : PubMed/NCBI

37 

DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, et al: NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet. 47:1475–1481. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, et al: Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet. 43:869–874. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Locasale JW: Serine, glycine and one-carbon units: Cancer metabolism in full circle. Nat Rev Cancer. 13:572–583. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Kamynina E, Lachenauer ER, DiRisio AC, Liebenthal RP, Field MS and Stover PJ: Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis. Proc Natl Acad Sci USA. 114:E2319–E2326. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Jin L, Li D, Alesi GN, Fan J, Kang HB, Lu Z, Boggon TJ, Jin P, Yi H, Wright ER, et al: Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth. Cancer Cell. 27:257–270. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Yelamanchi SD, Jayaram S, Thomas JK, Gundimeda S, Khan AA, Singhal A, Keshava Prasad TS, Pandey A, Somani BL and Gowda H: A pathway map of glutamate metabolism. J Cell Commun Signal. 10:69–75. 2016. View Article : Google Scholar :

43 

Choi YK and Park KG: Targeting glutamine metabolism for cancer treatment. Biomol Ther (Seoul). 26:19–28. 2018. View Article : Google Scholar :

44 

Vanhove K, Derveaux E, Graulus GJ, Mesotten L, Thomeer M, Noben JP, Guedens W and Adriaensens P: Glutamine addiction and therapeutic strategies in lung cancer. Int J Mol Sci. 20:2522019. View Article : Google Scholar : PubMed/NCBI

45 

Zhang B, Chen Y, Bao L and Luo W: GPT2 is induced by hypoxia-inducible factor (HIF)-2 and promotes glioblastoma growth. Cells. 11:25972022. View Article : Google Scholar : PubMed/NCBI

46 

Kim M, Gwak J, Hwang S, Yang S and Jeong SM: Mitochondrial GPT2 plays a pivotal role in metabolic adaptation to the perturbation of mitochondrial glutamine metabolism. Oncogene. 38:4729–4738. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Shen Y, Huang Q, Zhang Y, Hsueh CY and Zhou L: A novel signature derived from metabolism-related genes GPT and SMS to predict prognosis of laryngeal squamous cell carcinoma. Cancer Cell Int. 22:2262022. View Article : Google Scholar : PubMed/NCBI

48 

Ahn CS and Metallo CM: Mitochondria as biosynthetic factories for cancer proliferation. Cancer Metab. 3:12015. View Article : Google Scholar : PubMed/NCBI

49 

Krall AS, Xu S, Graeber TG, Braas D and Christofk HR: Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun. 7:114572016. View Article : Google Scholar : PubMed/NCBI

50 

Cai DJ, Zhang ZY, Bu Y, Li L, Deng YZ, Sun LQ, Hu CP and Li M: Asparagine synthetase regulates lung-cancer metastasis by stabilizing the β-catenin complex and modulating mitochondrial response. Cell Death Dis. 13:5662022. View Article : Google Scholar

51 

Ma G, Zhang Z, Li P, Zhang Z, Zeng M, Liang Z, Li D, Wang L, Chen Y, Liang Y and Niu H: Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment. Cell Commun Signal. 20:1142022. View Article : Google Scholar : PubMed/NCBI

52 

Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al: Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 481:380–384. 2011. View Article : Google Scholar : PubMed/NCBI

53 

Spinelli JB and Haigis MC: The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 20:745–754. 2018. View Article : Google Scholar : PubMed/NCBI

54 

Bertero T, Oldham WM, Grasset EM, Bourget I, Boulter E, Pisano S, Hofman P, Bellvert F, Meneguzzi G, Bulavin DV, et al: Tumor-stroma mechanics coordinate amino acid availability to sustain tumor growth and malignancy. Cell Metab. 29:124–140.e10. 2019. View Article : Google Scholar

55 

Sullivan LB, Gui DY, Hosios AM, Bush LN, Freinkman E and Vander Heiden MG: Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell. 162:552–563. 2015. View Article : Google Scholar : PubMed/NCBI

56 

Krall AS, Mullen PJ, Surjono F, Momcilovic M, Schmid EW, Halbrook CJ, Thambundit A, Mittelman SD, Lyssiotis CA, Shackelford DB, et al: Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth. Cell Metab. 33:1013–1026.e6. 2021. View Article : Google Scholar : PubMed/NCBI

57 

Newman AC and Maddocks ODK: One-carbon metabolism in cancer. Br J Cancer. 116:1499–1504. 2017. View Article : Google Scholar : PubMed/NCBI

58 

Li T, Song LL, Zhang YW, Han YL, Zhan ZY, Xv Z, Li Y, Tang Y, Yang Y, Wang S, et al: Molecular mechanism of c-Myc and PRPS1/2 against thiopurine resistance in Burkitt's lymphoma. J Cell Mol Med. 24:6704–6715. 2020. View Article : Google Scholar : PubMed/NCBI

59 

Macmillan AC, Karki B, Yang JC, Gertz KR, Zumwalde S, Patel JG, Czyzyk-Krzeska MF, Meller J and Cunningham JT: PRPS activity tunes redox homeostasis in Myc-driven lymphoma. Redox Biol. 84:1036492025. View Article : Google Scholar : PubMed/NCBI

60 

Liu T, Wang Z, Ye L, Duan Y, Jiang H, He H, Xiao L, Wu Q, Xia Y, Yang M, et al: Nucleus-exported CLOCK acetylates PRPS to promote de novo nucleotide synthesis and liver tumour growth. Nat Cell Biol. 25:273–284. 2023.PubMed/NCBI

61 

Song L, Li P, Sun H, Ding L, Wang J, Li B, Zhou BS, Feng H and Li Y: PRPS2 mutations drive acute lymphoblastic leukemia relapse through influencing PRPS1/2 hexamer stability. Blood Sci. 5:39–50. 2022. View Article : Google Scholar

62 

Lv Y, Wang X, Li X, Xu G, Bai Y, Wu J, Piao Y, Shi Y, Xiang R and Wang L: Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway. PLoS Biol. 18:e30008722020. View Article : Google Scholar : PubMed/NCBI

63 

Goswami MT, Chen G, Chakravarthi BV, Pathi SS, Anand SK, Carskadon SL, Giordano TJ, Chinnaiyan AM, Thomas DG, Palanisamy N, et al: Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer. Oncotarget. 6:23445–23461. 2015. View Article : Google Scholar : PubMed/NCBI

64 

Liu B, Song M, Qin H, Zhang B, Liu Y, Sun Y, Ma Y and Shi T: Phosphoribosyl Pyrophosphate amidotransferase promotes the progression of thyroid cancer via regulating pyruvate kinase M2. Onco Targets Ther. 13:7629–7639. 2020. View Article : Google Scholar : PubMed/NCBI

65 

Kitagawa Y, Kondo S, Fukuyo M, Wakae K, Dochi H, Mizokami H, Komura S, Kobayashi E, Hirai N, Ueno T, et al: Phosphoribosyl pyrophosphate amidotransferase: Novel biomarker and therapeutic target for nasopharyngeal carcinoma. Cancer Sci. 115:3587–3595. 2024. View Article : Google Scholar : PubMed/NCBI

66 

Ding M, Ma C, Lin Y, Fang H, Xu Y, Wang S, Chen Y, Zhou J, Gao H, Shan Y, et al: Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma. Cell Death Dis. 16:1792025. View Article : Google Scholar

67 

Huang F, Ni M, Chalishazar MD, Huffman KE, Kim J, Cai L, Shi X, Cai F, Zacharias LG, Ireland AS, et al: Inosine monophosphate dehydrogenase dependence in a subset of small cell lung cancers. Cell Metab. 28:369–382.e5. 2018. View Article : Google Scholar : PubMed/NCBI

68 

Zheng MM, Li JY, Guo HJ, Zhang J, Wang LS, Jiang KF, Wu HH, He QJ, Ding L and Yang B: IMPDH inhibitors upregulate PD-L1 in cancer cells without impairing immune checkpoint inhibitor efficacy. Acta Pharmacol Sin. 46:1058–1067. 2025. View Article : Google Scholar

69 

Zhao JZ, Wang W, Liu T, Zhang L, Lin DZ, Yao JY, Peng X, Jin G, Ma TT, Gao JB, et al: MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells. BMC Cancer. 22:12902022. View Article : Google Scholar : PubMed/NCBI

70 

Kofuji S, Hirayama A, Eberhardt AO, Kawaguchi R, Sugiura Y, Sampetrean O, Ikeda Y, Warren M, Sakamoto N, Kitahara S, et al: IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma. Nat Cell Biol. 21:1003–1014. 2019. View Article : Google Scholar : PubMed/NCBI

71 

Liu X, Wang J, Wu LJ, Trinh B and Tsai RYL: IMPDH inhibition decreases TERT expression and synergizes the cytotoxic effect of chemotherapeutic agents in glioblastoma cells. Int J Mol Sci. 25:59922024. View Article : Google Scholar : PubMed/NCBI

72 

Liu X, Sato N, Yabushita T, Li J, Jia Y, Tamura M, Asada S, Fujino T, Fukushima T, Yonezawa T, et al: IMPDH inhibition activates TLR-VCAM1 pathway and suppresses the development of MLL-fusion leukemia. EMBO Mol Med. 15:e156312023. View Article : Google Scholar :

73 

An S, Kumar R, Sheets ED and Benkovic SJ: Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science. 320:103–106. 2008. View Article : Google Scholar : PubMed/NCBI

74 

Deng Y, Gam J, French JB, Zhao H, An S and Benkovic SJ: Mapping protein-protein proximity in the purinosome. J Biol Chem. 287:36201–36207. 2012. View Article : Google Scholar : PubMed/NCBI

75 

Wu D, Yang S, Yuan C, Zhang K, Tan J, Guan K, Zeng H and Huang C: Targeting purine metabolism-related enzymes for therapeutic intervention: A review from molecular mechanism to therapeutic breakthrough. Int J Biol Macromol. 282:1368282024. View Article : Google Scholar : PubMed/NCBI

76 

Pedley AM, Pareek V and Benkovic SJ: The purinosome: A case study for a mammalian metabolon. Annu Rev Biochem. 91:89–106. 2022. View Article : Google Scholar : PubMed/NCBI

77 

Chan CY, Zhao H, Pugh RJ, Pedley AM, French J, Jones SA, Zhuang X, Jinnah H, Huang TJ and Benkovic SJ: Purinosome formation as a function of the cell cycle. Proc Natl Acad Sci USA. 112:1368–1373. 2015. View Article : Google Scholar : PubMed/NCBI

78 

Baresova V, Krijt M, Skopova V, Souckova O, Kmoch S and Zikanova M: CRISPR-Cas9 induced mutations along de novo purine synthesis in HeLa cells result in accumulation of individual enzyme substrates and affect purinosome formation. Mol Genet Metab. 119:270–277. 2016. View Article : Google Scholar : PubMed/NCBI

79 

Pelet A, Skopova V, Steuerwald U, Baresova V, Zarhrate M, Plaza JM, Hnizda A, Krijt M, Souckova O, Wibrand F, et al: PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome. Hum Mol Genet. 28:3805–3814. 2019. View Article : Google Scholar : PubMed/NCBI

80 

Chan CY, Pedley AM, Kim D, Xia C, Zhuang X and Benkovic SJ: Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria. Proc Natl Acad Sci USA. 115:13009–13014. 2018. View Article : Google Scholar : PubMed/NCBI

81 

French JB, Jones SA, Deng H, Pedley AM, Kim D, Chan CY, Hu H, Pugh RJ, Zhao H, Zhang Y, et al: Spatial colocalization and functional link of purinosomes with mitochondria. Science. 351:733–737. 2016. View Article : Google Scholar : PubMed/NCBI

82 

Pedley AM, Boylan JP, Chan CY, Kennedy EL, Kyoung M and Benkovic SJ: Purine biosynthetic enzymes assemble into liquid-like condensates dependent on the activity of chaperone protein HSP90. J Biol Chem. 298:1018452022. View Article : Google Scholar : PubMed/NCBI

83 

French JB, Zhao H, An SO, Niessen S, Deng YJ, Cravatt BF and Benkovic SJ: Hsp70/Hsp90 chaperone machinery is involved in the assembly of the purinosome. Proc Natl Acad Sci USA. 110:2528–2533. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Pedley AM, Karras GI, Zhang X, Lindquist S and Benkovic SJ: Role of HSP90 in the regulation of de novo purine biosynthesis. Biochemistry. 57:3217–3221. 2018. View Article : Google Scholar : PubMed/NCBI

85 

Yu J, Jin C, Su C, Moon D, Sun M, Zhang H, Jiang X, Zhang F, Tserentsoodol N, Bowie ML, et al: Resilience and vulnerabilities of tumor cells under purine shortage stress. Clin Cancer Res. 31:4345–4360. 2025. View Article : Google Scholar : PubMed/NCBI

86 

Stine ZE, Walton ZE, Altman BJ, Hsieh AL and Dang CV: MYC, metabolism, and cancer. Cancer Discov. 5:1024–1039. 2015. View Article : Google Scholar : PubMed/NCBI

87 

Wunder T and Mueller-Cajar O: Biomolecular condensates in photosynthesis and metabolism. Curr Opin Plant Biol. 58:1–7. 2020. View Article : Google Scholar : PubMed/NCBI

88 

Chou MC, Wang YH, Chen FY, Kung CY, Wu KP, Kuo JC, Chan SJ, Cheng ML, Lin CY, Chou YC, et al: PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly. Mol Cell. 83:4123–4140.e12. 2023. View Article : Google Scholar : PubMed/NCBI

89 

Cunningham JT, Moreno MV, Lodi A, Ronen SM and Ruggero D: Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer. Cell. 157:1088–1103. 2014. View Article : Google Scholar : PubMed/NCBI

90 

Camicia R, Winkler HC and Hassa PO: Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: A comprehensive review. Mol Cancer. 14:2072015. View Article : Google Scholar : PubMed/NCBI

91 

Delos Santos K, Kwon E and Moon NS: PRPS-associated disorders and the drosophila model of arts syndrome. Int J Mol Sci. 21:48242020. View Article : Google Scholar : PubMed/NCBI

92 

Zhang L, Zhao X, Hu J, Li T, Chen HZ, Zhang A, Wang H, Yu J and Zhang L: PRPS2 enhances RNA m6A methylation by stimulating SAM synthesis through enzyme-dependent and independent mechanisms. Nat Commun. 16:39662025. View Article : Google Scholar

93 

Jing XQ, Wang XJ, Zhang T, Zhu WC, Fang Y, Wu HX, Liu X, Ma D, Ji X, Jiang Y, et al: Cell-cycle-dependent phosphorylation of PRPS1 fuels nucleotide synthesis and promotes tumorigenesis. Cancer Res. 79:4650–4664. 2019. View Article : Google Scholar : PubMed/NCBI

94 

Zhuo W, Xia H, Lan B, Chen Y, Wang X and Liu J: Signature of immune-related metabolic genes predicts the prognosis of hepatocellular carcinoma. Front Immunol. 15:14813312024. View Article : Google Scholar : PubMed/NCBI

95 

Liu C, Knudsen GM, Pedley AM, He J, Johnson JL, Yaron TM, Cantley LC and Benkovic SJ: Mapping post-translational modifications of de novo purine biosynthetic enzymes: Implications for pathway regulation. J Proteome Res. 18:2078–2087. 2019. View Article : Google Scholar : PubMed/NCBI

96 

Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M and Nakayama KI: A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer. Nat Commun. 11:13202020. View Article : Google Scholar : PubMed/NCBI

97 

Xiang H, Kasajima R, Azuma K, Tagami T, Hagiwara A, Nakahara Y, Saito H, Igarashi Y, Wei F, Ban T, et al: Multi-omics analysis-based clinical and functional significance of a novel prognostic and immunotherapeutic gene signature derived from amino acid metabolism pathways in lung adenocarcinoma. Front Immunol. 15:13619922024. View Article : Google Scholar : PubMed/NCBI

98 

Loftus SK, Baxter LL, Cronin JC, Fufa TD; NISC Comparative Sequencing Program; Pavan WJ: Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis. Pigment Cell Melanoma Res. 30:339–532. 2017. View Article : Google Scholar : PubMed/NCBI

99 

Wu Z, Nguyen PT, Sondhi V, Yao RW, Lu Z, Dai T, Chiang JC, Cai F, Williams IM, Blatt EB, et al: NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT. Science. 390:1134–1142. 2025. View Article : Google Scholar : PubMed/NCBI

100 

Hedstrom L: IMP dehydrogenase: Structure, mechanism, and inhibition. Chem Rev. 109:2903–2928. 2009. View Article : Google Scholar : PubMed/NCBI

101 

Calise SJ and Chan EKL: Anti-rods/rings autoantibody and IMPDH filaments: An update after fifteen years of discovery. Autoimmun Rev. 19:1026432020. View Article : Google Scholar : PubMed/NCBI

102 

Kim HR, Roe JS, Lee JE, Hwang IY, Cho EJ and Youn HD: A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH. Biochem Biophys Res Commun. 418:682–688. 2012. View Article : Google Scholar : PubMed/NCBI

103 

Duan S, Huang W, Liu X, Liu X, Chen N, Xu Q, Hu Y, Song W and Zhou J: IMPDH2 promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways. J Exp Clin Cancer Res. 37:3042018. View Article : Google Scholar : PubMed/NCBI

104 

Casado P, Rio-Machin A, Miettinen JJ, Bewicke-Copley F, Rouault-Pierre K, Krizsan S, Parsons A, Rajeeve V, Miraki-Moud F, Taussig DC, et al: Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes. Signal Transduct Target Ther. 8:802023. View Article : Google Scholar : PubMed/NCBI

105 

Liu W, Li J, Xu S, Wang Y, Li J, Wang S, Fu L, Jiang M and Bai G: Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2. Phytomedicine. 134:1559552024. View Article : Google Scholar

106 

Kunjithapatham R and Ganapathy-Kanniappan S: GAPDH with NAD+-binding site mutation competitively inhibits the wild-type and affects glucose metabolism in cancer. Biochim Biophys Acta Gen Subj. 1862:2555–2563. 2018. View Article : Google Scholar : PubMed/NCBI

107 

Bie M, Tang Y, Xia Y, Zhang Q, Tian Y, Cheng C, Li X, Qi X and Kang F: HIF-1α mediates osteoclast-induced disuse osteoporosis via cytoophidia in the femur of mice. Bone. 168:1166482023. View Article : Google Scholar

108 

Ogawa-Iio A, Takeuchi K, Shigemi K, Genoveso MJ, Niitsu H, Koh I, Ota Y, Yamane K, Hinoi T, Osaka N, et al: IMPDH and GTP metabolism in cancer: Mechanisms, regulation, and translational scope. Cancer Sci. 116:3250–3265. 2025. View Article : Google Scholar : PubMed/NCBI

109 

Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Podar K, Le Gouill S, Shiraishi N, Yasui H, Roccaro AM, et al: Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway. Oncogene. 24:5888–5896. 2005. View Article : Google Scholar : PubMed/NCBI

110 

Tzoneva G, Dieck CL, Oshima K, Ambesi-Impiombato A, Sánchez-Martín M, Madubata CJ, Khiabanian H, Yu J, Waanders E, Iacobucci I, et al: Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia. Nature. 553:511–514. 2018. View Article : Google Scholar : PubMed/NCBI

111 

Grusch M, Rosenberger G, Fuhrmann G, Braun K, Titscher B, Szekeres T, Fritzer-Skekeres M, Oberhuber G, Krohn K, Hengstschlaeger M, et al: Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells. Cell Death Differ. 6:736–744. 1999. View Article : Google Scholar : PubMed/NCBI

112 

Tian Y, Zhang J, Chen L and Zhang X: The expression and prognostic role of IMPDH2 in ovarian cancer. Ann Diagn Pathol. 46:1515112020. View Article : Google Scholar : PubMed/NCBI

113 

Sugimoto A, Watanabe T, Matsuoka K, Okuno Y, Yanagi Y, Narita Y, Mabuchi S, Nobusue H, Sugihara E, Hirayama M, et al: Growth transformation of B cells by epstein-barr virus requires IMPDH2 induction and nucleolar hypertrophy. Microbiol Spectr. 11:e00440232023. View Article : Google Scholar : PubMed/NCBI

114 

Szwed A, Kim E and Jacinto E: Regulation and metabolic functions of mTORC1 and mTORC2. Physiol Rev. 101:1371–1426. 2021. View Article : Google Scholar : PubMed/NCBI

115 

Demetriades C, Plescher M and Teleman AA: Lysosomal recruitment of TSC2 is a universal response to cellular stress. Nat Commun. 7:106622016. View Article : Google Scholar : PubMed/NCBI

116 

Ben-Sahra I, Hoxhaj G, Ricoult SJH, Asara JM and Manning BD: mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle. Science. 351:728–733. 2016. View Article : Google Scholar : PubMed/NCBI

117 

Fontana F, Giannitti G, Marchesi S and Limonta P: The PI3K/Akt pathway and glucose metabolism: A dangerous liaison in cancer. Int J Biol Sci. 20:3113–3125. 2024. View Article : Google Scholar : PubMed/NCBI

118 

Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, et al: Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 39:171–183. 2010. View Article : Google Scholar : PubMed/NCBI

119 

Saha A, Connelly S, Jiang J, Zhuang S, Amador DT, Phan T, Pilz RB and Boss GR: Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis. Mol Cell. 55:264–276. 2014. View Article : Google Scholar : PubMed/NCBI

120 

Torrence ME, MacArthur MR, Hosios AM, Valvezan AJ, Asara JM, Mitchell JR and Manning BD: The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals. Elife. 10:e633262021. View Article : Google Scholar : PubMed/NCBI

121 

Mollaoglu G, Guthrie MR, Böhm S, Brägelmann J, Can I, Ballieu PM, Marx A, George J, Heinen C, Chalishazar MD, et al: MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to aurora kinase inhibition. Cancer Cell. 31:270–285. 2017. View Article : Google Scholar : PubMed/NCBI

122 

Liu YC, Li F, Handler J, Huang CR, Xiang Y, Neretti N, Sedivy JM, Zeller KI and Dang CV: Global regulation of nucleotide biosynthetic genes by c-Myc. PLoS One. 3:e27222008. View Article : Google Scholar : PubMed/NCBI

123 

Dang CV: MYC on the path to cancer. Cell. 149:22–35. 2012. View Article : Google Scholar : PubMed/NCBI

124 

Huang F, Huffman KE, Wang Z, Wang X, Li K, Cai F, Yang C, Cai L, Shih TS, Zacharias LG, et al: Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer. J Clin Invest. 131:e1399292021. View Article : Google Scholar :

125 

Ali ES, Lipońska A, O'Hara BP, Amici DR, Torno MD, Gao P, Asara JM, Yap MF, Mendillo ML and Ben-Sahra I: The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Mol Cell. 82:3284–3298.e7. 2022. View Article : Google Scholar : PubMed/NCBI

126 

Liu Y, Pareek V, Bhowmik D, Zhang X and Benkovic SJ: Purinosomes and lysosomes interact to maintain the purine pools. Int J Biochem Cell Biol. 186:1068302025. View Article : Google Scholar : PubMed/NCBI

127 

Valvezan AJ, Turner M, Belaid A, Lam HC, Miller SK, McNamara MC, Baglini C, Housden BE, Perrimon N, Kwiatkowski DJ, et al: mTORC1 couples nucleotide synthesis to nucleotide demand resulting in a targetable metabolic vulnerability. Cancer Cell. 32:6242017. View Article : Google Scholar : PubMed/NCBI

128 

Worby CA and Dixon JE: PTEN. Annu Rev Biochem. 83:641–669. 2014. View Article : Google Scholar : PubMed/NCBI

129 

Zuo Z, Liu J, Sun Z, Cheng YW, Ewing M, Bugge TH, Finkel T, Leppla SH and Liu S: ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth. Proc Natl Acad Sci USA. 120:e22119271202023. View Article : Google Scholar :

130 

Liefwalker DF, Ryan M, Wang Z, Pathak KV, Plaisier S, Shah V, Babra B, Dewson GS, Lai IK, Mosley AR, et al: Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies. Cancer Metab. 9:312021. View Article : Google Scholar : PubMed/NCBI

131 

Mannava S, Grachtchouk V, Wheeler LJ, Im M, Zhuang D, Slavina EG, Mathews CK, Shewach DS and Nikiforov MA: Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle. 7:2392–2400. 2008. View Article : Google Scholar : PubMed/NCBI

132 

Trejo-Solís C, Castillo-Rodríguez RA, Serrano-García N, Silva-Adaya D, Vargas-Cruz S, Chávez-Cortéz EG, Gallardo-Pérez JC, Zavala-Vega S, Cruz-Salgado A and Magaña-Maldonado R: Metabolic roles of HIF1, c-Myc, and p53 in glioma cells. Metabolites. 14:2492024. View Article : Google Scholar : PubMed/NCBI

133 

Liu W, Ding Z, Tao Y, Liu S, Jiang M, Yi F, Wang Z, Han Y, Zong H, Li D, et al: A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression. Mol Cancer. 23:1412024. View Article : Google Scholar : PubMed/NCBI

134 

Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, et al: Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 149:656–670. 2012. View Article : Google Scholar : PubMed/NCBI

135 

Santana-Codina N, Roeth AA, Zhang Y, Yang A, Mashadova O, Asara JM, Wang X, Bronson RT, Lyssiotis CA, Ying H and Kimmelman AC: Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis. Nat Commun. 9:49452018. View Article : Google Scholar : PubMed/NCBI

136 

Jiang X, Wang T, Zhao B, Sun H, Dong Y, Ma Y, Li Z, Wu Y, Wang K, Guan X, et al: KRASG12D-driven pentose phosphate pathway remodeling imparts a targetable vulnerability synergizing with MRTX1133 for durable remissions in PDAC. Cell Rep Med. 6:1019662025. View Article : Google Scholar

137 

Gao W, Xu Y, Chen T, Du Z, Liu X, Hu Z, Wei D, Gao C, Zhang W and Li Q: Targeting oxidative pentose phosphate pathway prevents recurrence in mutant Kras colorectal carcinomas. PLoS Biol. 17:e30004252019. View Article : Google Scholar : PubMed/NCBI

138 

Romero R, Sayin VI, Davidson SM, Bauer MR, Singh SX, LeBoeuf SE, Karakousi TR, Ellis DC, Bhutkar A, Sánchez-Rivera FJ, et al: Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med. 23:1362–1368. 2017. View Article : Google Scholar : PubMed/NCBI

139 

Krauß D, Moreno-Viedma V, Adachi-Fernandez E, de Sá Fernandes C, Genger JW, Fari O, Blauensteiner B, Kirchhofer D, Bradaric N, Gushchina V, et al: EGFR controls transcriptional and metabolic rewiring in KRAS(G12D) colorectal cancer. EMBO Mol Med. 17:1355–1392. 2025. View Article : Google Scholar

140 

Meena JK, Wang JH, Neill NJ, Keough D, Putluri N, Katsonis P, Koire AM, Lee H, Bowling EA, Tyagi S, et al: MYC induces oncogenic stress through RNA decay and ribonucleotide catabolism in breast cancer. Cancer Discov. 14:1699–1716. 2024. View Article : Google Scholar : PubMed/NCBI

141 

Ali ES, Sahu U, Villa E, O'Hara BP, Gao P, Beaudet C, Wood AW, Asara JM and Ben-Sahra I: ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis. Mol Cell. 78:1178–1191.e6. 2020. View Article : Google Scholar : PubMed/NCBI

142 

Cox AG, Hwang KL, Brown KK, Evason K, Beltz S, Tsomides A, O'Connor K, Galli GG, Yimlamai D, Chhangawala S, et al: Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol. 18:886–896. 2016. View Article : Google Scholar : PubMed/NCBI

143 

Fujita M, Orisaka M, Mizutani T, Fujita Y, Onuma T, Tsuyoshi H and Yoshida Y: YAP/TAZ Promote GLUT1 expression and are associated with prognosis in endometrial cancer. Cancers (Basel). 17:25542025. View Article : Google Scholar : PubMed/NCBI

144 

Gao C and Wang Y: YAP: The nexus between metabolism and cardiac remodeling. J Clin Invest. 132:e1576642022. View Article : Google Scholar : PubMed/NCBI

145 

Yu H, Tang H, Deng C, Lin Q, Yu P, Chen S and Ruan J: RRM2 improves cardiomyocyte proliferation after myocardial ischemia reperfusion Injury through the Hippo-YAP pathway. Dis Markers. 2021:50898722021. View Article : Google Scholar : PubMed/NCBI

146 

Shah SR, Ren C, Tippens ND, Park J, Mohyeldin A, Wang S, Vela G, Martinez-Gutierrez JC, Margolis SS, Schmidt S, et al: YAP controls cell migration and invasion through a Rho GTPase switch. Sci Signal. 18:eadu37942025.PubMed/NCBI

147 

Tu CE, Liu YF, Liu HW, Jiao CM, Liu Q, Hung MC, Li P, Wan XB, Fan XJ and Wang YL: D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint. J Hematol Oncol. 18:22025. View Article : Google Scholar : PubMed/NCBI

148 

Zhang H, Guo Z, Yi J, Wu J, Wang Y, Ren T, Zhang Y, Zhao H, Wu N, Wei G and Zhang D: Thymic egress and peripheral T cell homeostasis regulated by Rho GTPase-activating protein 30. Cell Death Differ. 32:2294–2308. 2025. View Article : Google Scholar : PubMed/NCBI

149 

Ahmad Mokhtar AM, Salikin NH, Haron AS, Amin-Nordin S, Hashim IF, Mohd Zaini Makhtar M, Zulfigar SB and Ismail NI: RhoG's role in T cell activation and function. Front Immunol. 13:8450642022. View Article : Google Scholar : PubMed/NCBI

150 

Cantrell DA: GTPases and T cell activation. Immunol Rev. 192:122–130. 2003. View Article : Google Scholar : PubMed/NCBI

151 

Chen L and Flies DB: Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 13:227–242. 2013. View Article : Google Scholar : PubMed/NCBI

152 

Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, Pierson Y, McNeill E, Longhi MS, Turnes BL, et al: The metabolite BH4 controls T cell proliferation in autoimmunity and cancer. Nature. 563:564–568. 2018. View Article : Google Scholar : PubMed/NCBI

153 

Madsen HB, Peeters MJ, Straten PT and Desler C: Nucleotide metabolism in the regulation of tumor microenvironment and immune cell function. Curr Opin Biotechnol. 84:1030082023. View Article : Google Scholar : PubMed/NCBI

154 

John SV, Seim GL, Erazo-Flores BJ, Votava JA, Urquiza US, Arp NL, Steill J, Freeman J, Carnevale LN, Roberts I, et al: Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide. Nat Metab. 7:1681–1702. 2025. View Article : Google Scholar : PubMed/NCBI

155 

Yang L, Li A, Yu W, Wang H, Zhang L, Wang D, Wang Y, Zhang R, Lei Q, Liu Z, et al: Blockade of purine metabolism reverses macrophage immunosuppression and enhances anti-tumor immunity in non-small cell lung cancer. Drug Resist Updat. 78:1011752025. View Article : Google Scholar

156 

Lu Y, Sun Q, Guan Q, Zhang Z, He Q, He J, Ji Z, Tian W, Xu X, Liu Y, et al: The XOR-IDH3α axis controls macrophage polarization in hepatocellular carcinoma. J Hepatol. 79:1172–1184. 2023. View Article : Google Scholar : PubMed/NCBI

157 

Shen J, Liao B, Gong L, Li S, Zhao J, Yang H, Gong Y and Li Y: CD39 and CD73: Biological functions, diseases and therapy. Mol Biomed. 6:972025. View Article : Google Scholar : PubMed/NCBI

158 

Zhang Y, Jin W, Deng Z, Gao B, Zhu Y, Fu J, Xu C, Wang W, Bai T, Jiao L, et al: Metabolic reprogramming nanomedicine potentiates colon cancer sonodynamic immunotherapy by inhibiting the CD39/CD73/ADO pathway. Acta Pharm Sin B. 15:2655–2672. 2025. View Article : Google Scholar : PubMed/NCBI

159 

Allard D, Cormery J, Bricha S, Fuselier C, Abbas Aghababazadeh F, Giraud L, Skora E, Haibe-Kains B and Stagg J: Adenosine uptake through the nucleoside transporter ENT1 suppresses antitumor immunity and T-cell pyrimidine synthesis. Cancer Res. 85:692–703. 2025. View Article : Google Scholar

160 

Yang H, Lei MML, Xie L, Shou Y and Lee TKW: Deciphering adenosine signaling in hepatocellular carcinoma: Pathways, prognostic models, and therapeutic implications. Clin Mol Hepatol. 31:706–729. 2025. View Article : Google Scholar : PubMed/NCBI

161 

He X, Cui J, Ma H, Abuduaini N, Huang Y, Tang L, Wang W, Zhang Y, Wang Y, Lu W, et al: Berberrubine is a novel and selective IMPDH2 inhibitor that impairs the growth of colorectal cancer. Biochem Pharmacol. 218:1158682023. View Article : Google Scholar : PubMed/NCBI

162 

Wang L, Yang R, Kong Y, Zhou J, Chen Y, Li R, Chen C, Tang X, Chen X, Xia J, et al: Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC. Int J Oral Sci. 16:442024. View Article : Google Scholar : PubMed/NCBI

163 

Liu SS, Li JS, Xue M, Wu WJ, Li X and Chen W: LncRNA UCA1 participates in de novo synthesis of guanine nucleotides in bladder cancer by recruiting TWIST1 to increase IMPDH1/2. Int J Biol Sci. 19:2599–2612. 2023. View Article : Google Scholar : PubMed/NCBI

164 

Burrell AL and Kollman JM: IMPDH dysregulation in disease: A mini review. Biochem Soc Trans. 50:71–82. 2022. View Article : Google Scholar : PubMed/NCBI

165 

Jia HW, Yang HL, Xiong ZL, Deng MH, Wang T, Liu Y and Cheng M: Design, synthesis and antitumor activity evaluation of novel indole acrylamide derivatives as IMPDH inhibitors. Bioorg Chem. 129:1062132022. View Article : Google Scholar : PubMed/NCBI

166 

Naffouje R, Grover P, Yu H, Sendilnathan A, Wolfe K, Majd N, Smith EP, Takeuchi K, Senda T, Kofuji S and Sasaki AT: Anti-tumor potential of IMP dehydrogenase inhibitors: A century-long story. Cancers (Basel). 11:13462019. View Article : Google Scholar : PubMed/NCBI

167 

Zerhouni M, Martin AR, Furstoss N, Gutierrez VS, Jaune E, Tekaya N, Beranger GE, Abbe P, Regazzetti C, Amdouni H, et al: Dual covalent inhibition of PKM and IMPDH targets metabolism in cutaneous metastatic melanoma. Cancer Res. 81:3806–3821. 2021. View Article : Google Scholar : PubMed/NCBI

168 

Sezaki M and Huang G: Repurposing immunosuppressants for antileukemia therapy. EMBO Mol Med. 15:e170422023. View Article : Google Scholar :

169 

Schnabel JL, Frost TC, Wang AC, Ananthapadmanabhan V, Gurram S, Soroko KM, Gokhale PC and DeCaprio JA: IMPDH inhibition induces DNA replication stress and ATR sensitivity in Merkel cell carcinoma. iScience. 28:1125672025. View Article : Google Scholar : PubMed/NCBI

170 

Tuncyurek P, Mayer JM, Klug F, Dillmann S, Henne-Bruns D, Keller F and Stracke S: Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: A novel adjunct to standard chemotherapy? Eur Surg Res. 39:380–387. 2007. View Article : Google Scholar : PubMed/NCBI

171 

Floryk D and Huberman E: Mycophenolic acid-induced replication arrest, differentiation markers and cell death of androgen-independent prostate cancer cells DU145. Cancer Lett. 231:20–29. 2006. View Article : Google Scholar

172 

Messina E, Micheli V and Giacomello A: Guanine nucleotide depletion induces differentiation and aberrant neurite outgrowth in human dopaminergic neuroblastoma lines: A model for basal ganglia dysfunction in Lesch-Nyhan disease. Neurosci Lett. 375:97–100. 2005. View Article : Google Scholar : PubMed/NCBI

173 

Dun B, Sharma A, Teng Y, Liu H, Purohit S, Xu H, Zeng L and She JX: Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways. PLoS One. 8:e817022013. View Article : Google Scholar : PubMed/NCBI

174 

Takebe N, Cheng X, Wu S, Bauer K, Goloubeva OG, Fenton RG, Heyman M, Rapoport AP, Badros A, Shaughnessy J, et al: Phase I clinical trial of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil (cellcept) in advanced multiple myeloma patients. Clin Cancer Res. 10:8301–8308. 2004. View Article : Google Scholar : PubMed/NCBI

175 

Rodríguez-Pascual J, Sha P, García-García E, Rajeshkumar NV, De Vicente E, Quijano Y, Cubillo A, Angulo B, Hernando O and Hidalgo M: A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer. Invest New Drugs. 31:14–19. 2013. View Article : Google Scholar

176 

Koonrungsesomboon N, Teeyakasem P, Dukaew N, Sirikaew N, Thongkumkoon P, Yongpitakwattana P, Thepbundit V, Chaiyawat P, Klangjorhor J, Sakuludomkan C, et al: Efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): A multicenter, phase II clinical trial. Int J Clin Oncol. 30:2362–2374. 2025. View Article : Google Scholar : PubMed/NCBI

177 

Torres-Diz M, Reglero C, Falkenstein CD, Castro A, Hayer KE, Radens CM, Quesnel-Vallières M, Ang Z, Sehgal P, Li MM, et al: An alternatively spliced gain-of-function NT5C2 isoform contributes to chemoresistance in acute lymphoblastic leukemia. Cancer Res. 84:3327–3336. 2024. View Article : Google Scholar : PubMed/NCBI

178 

De Clercq E: C-nucleosides to be revisited. J Med Chem. 59:2301–2311. 2016. View Article : Google Scholar

179 

Malek K, Boosalis MS, Waraska K, Mitchell BS and Wright DG: Effects of the IMP-dehydrogenase inhibitor, Tiazofurin, in bcr-abl positive acute myelogenous leukemia. Part I. In vivo studies. Leukemia Res. 28:1125–1136. 2004. View Article : Google Scholar

180 

Tricot GJ, Jayaram HN, Lapis E, Natsumeda Y, Nichols CR, Kneebone P, Heerema N, Weber G and Hoffman R: Biochemically directed therapy of leukemia with tiazofurin, a selective blocker of inosine 5'-phosphate dehydrogenase activity. Cancer Res. 49:3696–3701. 1989.PubMed/NCBI

181 

Melink TJ, Von Hoff DD, Kuhn JG, Hersh MR, Sternson LA, Patton TF, Siegler R, Boldt DH and Clark GM: Phase I evaluation and pharmacokinetics of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). Cancer Res. 45:2859–2865. 1985.PubMed/NCBI

182 

Maroun JA and Stewart DJ: Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). Invest New Drugs. 8(Suppl 1): S33–S39. 1990. View Article : Google Scholar : PubMed/NCBI

183 

Stewart DJ, Eisenhauer E, Macdonald DR, Cairncross JG and Langleben A: Phase II study of tiazofurin in gliomas in adults. A national cancer institute of Canada study. J Neurooncol. 15:175–179. 1993. View Article : Google Scholar : PubMed/NCBI

184 

Jayaram HN, Yalowitz JA, Arguello F and Greene JF Jr: Toxicity and efficacy of benzamide riboside in cancer chemotherapy models. Curr Med Chem. 9:787–792. 2002. View Article : Google Scholar : PubMed/NCBI

185 

Szekeres T, Sedlak J and Novotny L: Benzamide riboside, a recent inhibitor of inosine 5'-monophosphate dehydrogenase induces transferrin receptors in cancer cells. Curr Med Chem. 9:759–764. 2002. View Article : Google Scholar : PubMed/NCBI

186 

Gharehbaghi K, Sreenath A, Hao Z, Paull KD, Szekeres T, Cooney DA, Krohn K and Jayaram HN: Comparison of biochemical parameters of benzamide riboside, a new inhibitor of IMP dehydrogenase, with tiazofurin and selenazofurin. Biochem Pharmacol. 48:1413–1419. 1994. View Article : Google Scholar : PubMed/NCBI

187 

Jain J, Ma JG, Furey B, Recher C, Demur C, Poondru S, Zhang J, Li S, Firestone B, Olson K, et al: The IMPDH inhibitor VX-944 demonstrates in vivo efficacy in an aggressive leukemia model. Blood. 104:25302004. View Article : Google Scholar

188 

Hamilton JM, Harding MW, Genna T and Bol DK: A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers. J Clin Pharmacol. 49:30–38. 2009. View Article : Google Scholar

189 

Garcia-Manero G, Pemmaraju N, Alvarado Y, Naqvi K, Ravandi F, Jabbour E, De Lumpa R, Kantarjian H, Advani A, Mukherjee S, et al: Results of a phase 1/2a dose-escalation study of FF-10501-01, an IMPDH inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndromes. Leuk Lymphoma. 61:1943–1953. 2020. View Article : Google Scholar : PubMed/NCBI

190 

Yang H, Fang Z, Wei Y, Bohannan ZS, Gañán-Gómez I, Pierola AA, Paradiso LJ, Iwamura H and Garcia-Manero G: Preclinical activity of FF-10501-01, a novel inosine-5'-monophosphate dehydrogenase inhibitor, in acute myeloid leukemia. Leuk Res. 59:85–92. 2017. View Article : Google Scholar : PubMed/NCBI

191 

Ichii M, Oritani K, Murase M, Komatsu K, Yamazaki M, Kyoden R, Kito N, Nozaki Y, Saito M, Iwamura H and Kanakura Y: Molecular targeting of inosine-5'-monophosphate dehydrogenase by FF-10501 promotes erythropoiesis via ROS/MAPK pathway. Leuk Lymphoma. 59:448–459. 2018. View Article : Google Scholar

192 

Levine AM, Shimodaira S and Lai MMC: Treatment of HCV-related mantle-cell lymphoma with ribavirin and pegylated interferon alfa. New Engl J Med. 349:2078–2079. 2003. View Article : Google Scholar : PubMed/NCBI

193 

Borden KLB and Culjkovic-Kraljacic B: Ribavirin as an anti-cancer therapy: Acute myeloid leukemia and beyond? Leuk Lymphoma. 51:1805–1815. 2010. View Article : Google Scholar : PubMed/NCBI

194 

Dunn LA, Fury MG, Sherman EJ, Ho AA, Katabi N, Haque SS and Pfister DG: Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer. Head Neck. 40:233–241. 2018. View Article : Google Scholar

195 

Casaos J, Gorelick NL, Huq S, Choi J, Xia Y, Serra R, Felder R, Lott T, Kast RE, Suk I, et al: The use of ribavirin as an anticancer therapeutic: Will it go viral? Mol Cancer Ther. 18:1185–1194. 2019. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhu H, Wang H, Li X, Zhang W, Wang Y, Tan Q, Ying D, Shi Z and Song J: IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review). Int J Mol Med 57: 81, 2026.
APA
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q. ... Song, J. (2026). IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review). International Journal of Molecular Medicine, 57, 81. https://doi.org/10.3892/ijmm.2026.5752
MLA
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q., Ying, D., Shi, Z., Song, J."IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review)". International Journal of Molecular Medicine 57.4 (2026): 81.
Chicago
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q., Ying, D., Shi, Z., Song, J."IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 81. https://doi.org/10.3892/ijmm.2026.5752
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu H, Wang H, Li X, Zhang W, Wang Y, Tan Q, Ying D, Shi Z and Song J: IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review). Int J Mol Med 57: 81, 2026.
APA
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q. ... Song, J. (2026). IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review). International Journal of Molecular Medicine, 57, 81. https://doi.org/10.3892/ijmm.2026.5752
MLA
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q., Ying, D., Shi, Z., Song, J."IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review)". International Journal of Molecular Medicine 57.4 (2026): 81.
Chicago
Zhu, H., Wang, H., Li, X., Zhang, W., Wang, Y., Tan, Q., Ying, D., Shi, Z., Song, J."IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 81. https://doi.org/10.3892/ijmm.2026.5752
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