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Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor

  • Authors:
    • Loredana Vesci
    • Ferdinando Maria Milazzo
    • Valeria Carollo
    • Silvia Pace
    • Giuseppe Giannini
  • View Affiliations / Copyright

    Affiliations: Research & Development, Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, Italy
    Copyright: © Vesci et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1421-1429
    |
    Published online on: August 1, 2014
       https://doi.org/10.3892/ijo.2014.2575
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Abstract

4-Amino substituted resorcino-isoxazole (SST0116CL1) (property of Sigma-Tau Research Switzerland S.A.) is a potent, second generation, small-molecule heat shock protein 90 inhibitor (Hsp90i). SST0116CL1 binds to the ATP binding pocket of Hsp90, and interferes with Hsp90 chaperone function thus resulting in client protein degradation and tumor growth inhibition. The aim of the study was to assess SST0116CL1 in various solid and haematological tumors. The antitumor properties of SST0116CL1 were assessed using in vitro cell proliferation and client protein degradation assays and in vivo different tumor xenograft models. Pharmacokinetic (PK) data were also generated in tumor-bearing mice to gain an understanding of optimal dosing schedules and regimens. SST0116CL1 was shown to inhibit recombinant Hsp90α and to induce the destabilization of different client proteins, often overexpressed and constitutively activated in different types of hematological or solid human tumors. In preclinical in vivo studies, it was revealed to induce antitumor effects in murine models of leukemia and of gastric and ovarian carcinoma. A modulation of PD biomarkers in terms of downregulation of Hsp90 client proteins in tumor-bearing mice was found. SST0116CL1 is a new clinical candidate for cancer therapy. The antitumor property of SST0116CL1, likely due to direct inhibition of the Hsp90 enzymatic activity, may prove to be a critical attribute as the compound enters phase I clinical trials.
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View References

1 

Li J and Buchner J: Structure, function, and regulation of the Hsp90 machinery. Biomed J. 36:106–117. 2013. View Article : Google Scholar

2 

Hao H, Naomoto Y, Bao X, Watanabe N, Sakurama K, Noma K, Motoki T, Tomono Y, Fukazawa T, Shirakawa Y, Yamatsuji T, Matsuoka J and Takaoka M: Hsp90 and its inhibitors. Oncol Rep. 23:1483–1492. 2010.PubMed/NCBI

3 

Whitesell L and Lindquist SL: HSP90 and the chaperoning of cancer. Nat Rev Cancer. 5:761–772. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Mahalingam D, Swords R, Carew JS, Nawrocki ST, Bhalla K and Gilles FJ: Targeting HSP90 for cancer therapy. Br J Cancer. 100:1523–1529. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, Neckers L and Trepel JB: Update on Hsp90 inhibitors in clinical trial. Curr Top Med Chem. 9:1479–1492. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Sessa C, Shapiro GI, Bhalla KN, Britten C, Jacks KS, Mita M, Papadimitrakopoulou V, Pluard T, Samuel TA, Akimov M, Quadt C, Fernandez-Ibarra C, Lu H, Bailey S, Chica S and Banerji U: First-in-human phase I dose-escalation study of the Hsp90 inhibitor AUY922 in patients with advanced solid tumors. Clin Cancer Res. 19:3671–3680. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Goldman JW, Raju RN, Gordon GA, El-Hariry I, Teofilivici F, Vukovic VM, Bradley R, Karol MD, Chen Y, Guo W, Inoue T and Rosen LS: A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies. Biomed Central Cancer. 13:152–161. 2013.

8 

Soga S, Akinaga S and Shiotsu Y: Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Curr Pharm Des. 19:366–376. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Li J, Soroka J and Buchner J: The Hsp90 chaperone machinery: conformational dynamics and regulation by co-chaperons. Biochim Biophys Acta. 1823.624–635. 2012.PubMed/NCBI

10 

Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, Patterson L, de Haven Brandon A, Gowan S, Boxall F, Aherne W, Rowlands M, Hayes A, Martins V, Urban F, Boxall K, Prodromou C, Pearl L, James K, Matthews TP, Cheung KM, Kalusa A, Jones K, McDonald E, Barril X, Brough PA, Cansfield JE, Dymock B, Drysdale MJ, Finch H, Howes R, Hubbard RE, Surgenor A, Webb P, Wood M, Wright L and Workman P: NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res. 68:2850–2860. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Jensen MR, Schoepfer J, Radimerski T, Massey A, Guy CT, Brueggen J, Quadt C, Buckler A, Cozens R, Drysdale MJ, Garcia-Echeverria C and Chène P: NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res. 10:R332008. View Article : Google Scholar : PubMed/NCBI

12 

Wang Y, Trepel JB, Neckers LM and Giaccone G: STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs. 11:1466–1476. 2010.PubMed/NCBI

13 

Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S and Anderson KC: SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 113:846–855. 2009. View Article : Google Scholar

14 

Lin TY, Bear M, Du Z, Foley KP, Ying W, Barsoum J and London C: The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors. Exp Hematol. 36:1266–1277. 2008. View Article : Google Scholar

15 

Lundgren K, Zhang H, Brekken J, Huser N, Powell RE, Timple N, Busch DJ, Neely L, Sensintaffar JL, Yang YC, McKenzie A, Friedman J, Scannevin R, Kamal A, Hong K, Kasibhatla SR, Boehm MF and Burrows FJ: BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol Cancer Ther. 8:921–929. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Picard D: Heat shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci. 59:1640–1648. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Baruchello R, Simoni D, Grisolia G, Barbato G, Marchetti P, Rondanin R, Mangiola S, Giannini G, Brunetti T, Alloatti D, Gallo G, Ciacci A, Vesci L, Castorina M, Milazzo FM, Cervoni ML, Guglielmi MB, Barbarino M, Foderà R, Pisano C and Cabri W: Novel 3.4-isoxazolediamides as potent inhibitors of chaperone heat shock protein 90. J Med Chem. 54:8592–8604. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Jhaveri K and Modi S: Hsp90 inhibitors for cancer therapy and overcoming drug resistance. Adv Pharmacol. 65:471–517. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Patel HJ, Modi S, Chiosis G and Taldone T: Advances in the discovery and development of heat-shock protein 90 inhibitors for cancer treatment. Expert Opin Drug Discov. 6:559–587. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Trepel J, Mollapour M, Giaccone G and Neckers L: Targeting the dynamic Hsp90 complex in cancer. Nat Rev Cancer. 10:537–549. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Ramanathan RK and Egorin MJ, Eiseman JL, Ramalingam S, Friedland D, Agarwala SS, Zuhowski EG, Lan J, Potter DM, Ivy SP, Ramalingam S, Brufsky AM, Wong MK, Tutchko S and Egorin MJ: Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygenldanamycin in adult patients with refractory advanced cancers. Clin Cancer Res. 13:1769–1774. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Ramanathan RK, Egorin MJ, Erlichman C, Remick SC, Ramalingam SS, Naret C, Holleran JL, TenEyck CJ, Ivy SP and Belani CP: Phase I pharmacokinetic and pharmacodynamic study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90, in patients with advanced solid tumors. J Clin Oncol. 28:1520–1526. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Mimnaugh EG, Chavany C and Neckers L: Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem. 271:22796–22801. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Christensen JG, Schreck R, Burrows J, Kuruganti P, Chan E, Le P, Chen J, Wang X, Ruslim L, Blake R, Lipson KE, Ramphal J, Do S, Cui JJ, Cherrington JM and Mendel DB: A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 63:7345–7355. 2003.PubMed/NCBI

25 

Gilliland DG and Griffin JD: Role of FLT3 in leukemia. Curr Opin Hematol. 9:274–281. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Lopes de Menezes DE, Peng J, Garrett EN, Louie SG, Lee SH, Wiesmann M, Tang Y, Shephard L, Goldbeck C, Oei Y, Ye H, Aukerman SL and Heise C: CHIR-258: a potent inhibitor of FLT3 kinase in experimental tumor xenograft model of human acute myelogenous leukemia. Clin Cancer Res. 11:5281–5291. 2005.PubMed/NCBI

27 

Fathi AT and Chabner BA: FLT3 inhibition as therapy in acute myeloid leukemia: a record of trials and tribulations. Oncologist. 16:1162–1174. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Gottesman MM, Bates SE and Fojo T: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI

29 

McCollum AK, TenEyck CJ, Stensgard B, Morlan BW, Ballman KV, Jenkins RB, Toft DO and Erlichman C: P-glycoprotein mediated resistance to Hsp90-directed therapy is eclipsed by the heat shock response. Cancer Res. 68:7419–7427. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Banerji U, O’Donnell A, Scurr M, Pacey S, Stapleton S, Asad Y, Simmons L, Maloney A, Raynaud F, Campbell M, Walton M, Lakhani S, Kaye S, Workman P and Judson I: Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J Clin Oncol. 23:4152–4161. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Kelland LR, Sharp SY, Rogers PM, Myers TG and Workman P: DT Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J Natl Cancer Inst. 91:1940–1949. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Hostein I, Robertson D, DiStefano F, Workman P and Clarke PA: Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res. 61:4003–4009. 2001.PubMed/NCBI

33 

Ellis LM and Hicklin DJ: Resistance to targeted therapies: refining anticancer therapy in the era of molecular oncology. Clin Cancer Res. 15:7471–7478. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Vesci L, Milazzo FM, Carollo V, Pace S and Giannini G: Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor. Int J Oncol 45: 1421-1429, 2014.
APA
Vesci, L., Milazzo, F.M., Carollo, V., Pace, S., & Giannini, G. (2014). Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor. International Journal of Oncology, 45, 1421-1429. https://doi.org/10.3892/ijo.2014.2575
MLA
Vesci, L., Milazzo, F. M., Carollo, V., Pace, S., Giannini, G."Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor". International Journal of Oncology 45.4 (2014): 1421-1429.
Chicago
Vesci, L., Milazzo, F. M., Carollo, V., Pace, S., Giannini, G."Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor". International Journal of Oncology 45, no. 4 (2014): 1421-1429. https://doi.org/10.3892/ijo.2014.2575
Copy and paste a formatted citation
x
Spandidos Publications style
Vesci L, Milazzo FM, Carollo V, Pace S and Giannini G: Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor. Int J Oncol 45: 1421-1429, 2014.
APA
Vesci, L., Milazzo, F.M., Carollo, V., Pace, S., & Giannini, G. (2014). Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor. International Journal of Oncology, 45, 1421-1429. https://doi.org/10.3892/ijo.2014.2575
MLA
Vesci, L., Milazzo, F. M., Carollo, V., Pace, S., Giannini, G."Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor". International Journal of Oncology 45.4 (2014): 1421-1429.
Chicago
Vesci, L., Milazzo, F. M., Carollo, V., Pace, S., Giannini, G."Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor". International Journal of Oncology 45, no. 4 (2014): 1421-1429. https://doi.org/10.3892/ijo.2014.2575
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