Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
World Academy of Sciences Journal
Join Editorial Board Propose a Special Issue
Print ISSN: 2632-2900 Online ISSN: 2632-2919
Journal Cover
May-June 2023 Volume 5 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-June 2023 Volume 5 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Biological applications of imiquimod analogues: An update (Review)

  • Authors:
    • Joelle Obeid
    • Abdullah Shaito
    • Hiba El Hajj
    • Carine Deleuze‑masquefa
    • Pierre-Antoine Bonnet
    • Marwan El‑Sabban
    • Jessica Saliba
  • View Affiliations / Copyright

    Affiliations: Sorbonne University, INSERM, Nutrition and Obesity: Systemic Approaches, Nutriomics, 75006 Paris, France, Biomedical Research Center, Department of Biomedical Sciences at College of Health Sciences, and College of Medicine, Qatar University, Doha 2713, Qatar, Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, Beirut 1107, Lebanon, Institute of Biomolecules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Faculty of Pharmacy, Balard Chemistry Unit, Montpellier University, 34090 Montpellier, France, Institute of Biomolecules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Faculty of Pharmacy, Balard Chemistry Unit, Montpellier University, 34090 Montpellier, France, Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon, Department of Biology, Faculty of Sciences, Lebanese University, Beirut 1533, Lebanon
    Copyright: © Obeid et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 20
    |
    Published online on: June 30, 2023
       https://doi.org/10.3892/wasj.2023.197
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The last decade witnessed intensive efforts in drug discovery and the emergence of thousands of molecules with potential for use as therapeutic targets. However, only a few hundred of these molecules reached the stage of clinical trials, with only a handful being translated from the bench to bedside. One such example is imiquimod, an immune response modifier belonging to the imidazoquinoline family. Imiquimod was first approved by the US Food and Drug Administration for the topical treatment of anal and genital warts and actinic keratosis, and later exhibited a potent antitumor activity. This promising activity inspired the development of several imidazoquinoxaline analogues and derivatives. The present review provides a comprehensive overview of the scientific literature on the chemical synthesis of imiquimod and several of its analogues, namely EAPB0203, EAPB0503 and EABP02303. The present review also discusses their preclinical properties and mechanisms of action in the context of cancer and parasitic infections, highlighting the worthiness of translating these activities into therapeutic drugs.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Dunn GP, Old LJ and Schreiber RD: The three Es of cancer immunoediting. Annu Rev Immunol. 22:329–360. 2004.PubMed/NCBI View Article : Google Scholar

2 

Abbott M and Ustoyev Y: Cancer and the immune system: The history and background of immunotherapy. Semin Oncol Nurs. 35(150923)2019.PubMed/NCBI View Article : Google Scholar

3 

Kennedy LB and Salama AKS: A review of cancer immunotherapy toxicity. CA Cancer J Clin. 70:86–104. 2020.PubMed/NCBI View Article : Google Scholar

4 

Avorn J: Learning about the safety of drugs-a half-century of evolution. N Engl J Med. 365:2151–2153. 2011.PubMed/NCBI View Article : Google Scholar

5 

Wu Y, Yang Z, Cheng K, Bi H and Chen J: Small molecule-based immunomodulators for cancer therapy. Acta Pharm Sin B. 12:4287–4308. 2022.PubMed/NCBI View Article : Google Scholar

6 

Kumar AR, Devan AR, Nair B, Vinod BS and Nath LR: Harnessing the immune system against cancer: Current immunotherapy approaches and therapeutic targets. Mol Biol Rep. 48:8075–8095. 2021.PubMed/NCBI View Article : Google Scholar

7 

Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, Carpeno JD, Califano R, Nishio M, et al: Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 39:619–630. 2021.PubMed/NCBI View Article : Google Scholar

8 

Vaddepally RK, Kharel P, Pandey R, Garje R and Chandra AB: Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel). 12(738)2020.PubMed/NCBI View Article : Google Scholar

9 

Chen XY, Li YD, Xie Y, Cao LQ, Ashby CR Jr, Zhao H and Chen ZS: Nivolumab and relatlimab for the treatment of melanoma. Drugs Today (Barc). 59:91–104. 2023.PubMed/NCBI View Article : Google Scholar

10 

Kang C: Retifanlimab: First approval. Drugs. 83:731–737. 2023.PubMed/NCBI View Article : Google Scholar

11 

Di Trolio R, Simeone E, Di Lorenzo G, Grimaldi AM, Romano A, Ayala F, Caracò C, Mozzillo N and Ascierto PA: Update on PEG-interferon α-2b as adjuvant therapy in melanoma. Anticancer Res. 32:3901–3909. 2012.PubMed/NCBI

12 

Qureshi YA, Karp CL and Dubovy SR: Intralesional interferon alpha-2b therapy for adnexal Kaposi sarcoma. Cornea. 28:941–943. 2009.PubMed/NCBI View Article : Google Scholar

13 

Rallis KS, Corrigan AE, Dadah H, George AM, Keshwara SM, Sideris M and Szabados B: Cytokine-based cancer immunotherapy: Challenges and opportunities for IL-10. Anticancer Res. 41:3247–3252. 2021.PubMed/NCBI View Article : Google Scholar

14 

Lamb YN: Pexidartinib: First Approval. Drugs. 79:1805–1812. 2019.PubMed/NCBI View Article : Google Scholar

15 

Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K and Akira S: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 3:196–200. 2002.PubMed/NCBI View Article : Google Scholar

16 

Kamath P, Darwin E, Arora H and Nouri K: A review on imiquimod therapy and discussion on optimal management of basal cell carcinomas. Clin Drug Investig. 38:883–899. 2018.PubMed/NCBI View Article : Google Scholar

17 

Tyring S: Imiquimod applied topically: A novel immune response modifier. Skin Therapy Lett. 6:1–4. 2001.PubMed/NCBI

18 

Courbet A, Bec N, Constant C, Larroque C, Pugniere M, Messaoudi SE, Zghaib Z, Khier S, Deleuze-Masquefa C and Gattacceca F: Imidazoquinoxaline anticancer derivatives and imiquimod interact with tubulin: Characterization of molecular microtubule inhibiting mechanisms in correlation with cytotoxicity. PLoS One. 12(e0182022)2017.PubMed/NCBI View Article : Google Scholar

19 

Moarbess G, Deleuze-Masquefa C, Bonnard V, Gayraud-Paniagua S, Vidal JR, Bressolle F, Pinguet F and Bonnet PA: In vitro and in vivo anti-tumoral activities of imidazo[1,2-a]quinoxaline, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline derivatives. Bioorg Med Chem. 16:6601–6610. 2008.PubMed/NCBI View Article : Google Scholar

20 

Deleuze-Masquefa C, Moarbess G, Khier S, David N, Gayraud-Paniagua S, Bressolle F, Pinguet F and Bonnet PA: New imidazo[1,2-a]quinoxaline derivatives: Synthesis and in vitro activity against human melanoma. Eur J Med Chem. 44:3406–3411. 2009.PubMed/NCBI View Article : Google Scholar

21 

Kwong A, Sanlorenzo M, Rappersberger K and Vujic I: Update on advanced melanoma treatments: Small molecule targeted therapy, immunotherapy, and future combination therapies. Wien Med Wochenschr. 169:314–322. 2019.PubMed/NCBI View Article : Google Scholar

22 

Zghaib Z, Guichou JF, Vappiani J, Bec N, Hadj-Kaddour K, Vincent LA, Paniagua-Gayraud S, Larroque C, Moarbess G, Cuq P, et al: New imidazoquinoxaline derivatives: Synthesis, biological evaluation on melanoma, effect on tubulin polymerization and structure-activity relationships. Bioorg Med Chem. 24:2433–2440. 2016.PubMed/NCBI View Article : Google Scholar

23 

Moarbess G, El-Hajj H, Kfoury Y, El-Sabban ME, Lepelletier Y, Hermine O, Deleuze-Masquéfa C, Bonnet PA and Bazarbachi A: EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I-associated adult T-cell leukemia/lymphoma. Blood. 111:3770–3777. 2008.PubMed/NCBI View Article : Google Scholar

24 

Saliba J, Deleuze-Masquéfa C, Iskandarani A, El Eit R, Hmadi R, Mahon FX, Bazarbachi A, Bonnet PA and Nasr R: EAPB0503, a novel imidazoquinoxaline derivative, inhibits growth and induces apoptosis in chronic myeloid leukemia cells. Anticancer Drugs. 25:624–632. 2014.PubMed/NCBI View Article : Google Scholar

25 

Nabbouh AI, Hleihel RS, Saliba JL, Karam MM, Hamie MH, Wu HCJM, Berthier CP, Tawil NM, Bonnet PAA, Deleuze-Masquefa C and El Hajj HA: Imidazoquinoxaline derivative EAPB0503: A promising drug targeting mutant nucleophosmin 1 in acute myeloid leukemia. Cancer. 123:1662–1673. 2017.PubMed/NCBI View Article : Google Scholar

26 

El Hajj R, Youness HB, Lachaud L, Bastien P, Masquefa C, Bonnet PA, El Hajj H and Khalifeh I: EAPB0503: An Imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica. PLoS Negl Trop Dis. 12(e0006854)2018.PubMed/NCBI View Article : Google Scholar

27 

Baumann M and Baxendale IR: An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles. Beilstein J Org Chem. 9:2265–2319. 2013.PubMed/NCBI View Article : Google Scholar

28 

Rudy SJ: Imiquimod (Aldara): Modifying the immune response. Dermatol Nurs. 14:268–270. 2002.PubMed/NCBI

29 

Miller RL, Gerster JF, Owens ML, Slade HB and Tomai MA: Imiquimod applied topically: A novel immune response modifier and new class of drug. Int J Immunopharmacol. 21:1–14. 1999.PubMed/NCBI View Article : Google Scholar

30 

Smith KJ, Hamza S and Skelton H: The imidazoquinolines and their place in the therapy of cutaneous disease. Expert Opin Pharmacother. 4:1105–1119. 2003.PubMed/NCBI View Article : Google Scholar

31 

Deleuze-Masquefa C, Gerebtzoff G, Subra G, Fabreguettes JR, Ovens A, Carraz M, Strub MP, Bompart J, George P and Bonnet PA: Design and synthesis of novel imidazo[1,2-a]quinoxalines as PDE4 inhibitors. Bioorg Med Chem. 12:1129–1139. 2004.PubMed/NCBI View Article : Google Scholar

32 

Del Rosso JQ: Topical imiquimod therapy for actinic keratosis: Is long-term clearance a realistic benefit? J Clin Aesthet Dermatol. 1:44–47. 2008.PubMed/NCBI

33 

Oumata N, Nguyen PH, Beringue V, Soubigou F, Pang Y, Desban N, Massacrier C, Morel Y, Paturel C, Contesse MA, et al: The toll-like receptor agonist imiquimod is active against prions. PLoS One. 8(e72112)2013.PubMed/NCBI View Article : Google Scholar

34 

Sidky YA, Borden EC, Weeks CE, Reiter MJ, Hatcher JF and Bryan GT: Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine. Cancer Res. 52:3528–3533. 1992.PubMed/NCBI

35 

Sauder DN, Skinner RB, Fox TL and Owens ML: Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations. Sex Transm Dis. 30:124–128. 2003.PubMed/NCBI View Article : Google Scholar

36 

Yokogawa M, Takaishi M, Nakajima K, Kamijima R, Digiovanni J and Sano S: Imiquimod attenuates the growth of UVB-induced SCC in mice through Th1/Th17 cells. Mol Carcinog. 52:760–769. 2013.PubMed/NCBI View Article : Google Scholar

37 

Spaner DE, Miller RL, Mena J, Grossman L, Sorrenti V and Shi Y: Regression of lymphomatous skin deposits in a chronic lymphocytic leukemia patient treated with the toll-like receptor-7/8 agonist, imiquimod. Leuk Lymphoma. 46:935–939. 2005.PubMed/NCBI View Article : Google Scholar

38 

Raman VS, Duthie MS, Fox CB, Matlashewski G and Reed SG: Adjuvants for Leishmania vaccines: From models to clinical application. Front Immunol. 3(144)2012.PubMed/NCBI View Article : Google Scholar

39 

Hamie M, Najm R, Deleuze-Masquefa C, Bonnet PA, Dubremetz JF, El Sabban M and El Hajj H: Imiquimod targets toxoplasmosis through modulating host toll-like receptor-MyD88 signaling. Front Immunol. 12(629917)2021.PubMed/NCBI View Article : Google Scholar

40 

Arevalo I, Ward B, Miller R, Meng TC, Najar E, Alvarez E, Matlashewski G and Llanos-Cuentas A: Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 33:1847–1851. 2001.PubMed/NCBI View Article : Google Scholar

41 

Miranda-Verastegui C, Tulliano G, Gyorkos TW, Calderon W, Rahme E, Ward B, Cruz M, Llanos-Cuentas A and Matlashewski G: First-line therapy for human cutaneous leishmaniasis in Peru using the TLR7 agonist imiquimod in combination with pentavalent antimony. PLoS Negl Trop Dis. 3(e491)2009.PubMed/NCBI View Article : Google Scholar

42 

Arevalo I, Tulliano G, Quispe A, Spaeth G, Matlashewski G, Llanos-Cuentas A and Pollack H: Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis. Clin Infect Dis. 44:1549–1554. 2007.PubMed/NCBI View Article : Google Scholar

43 

Walter A, Schäfer M, Cecconi V, Matter C, Urosevic-Maiwald M, Belloni B, Schönewolf N, Dummer R, Bloch W, Werner S, et al: Aldara activates TLR7-independent immune defence. Nat Commun. 4(1560)2013.PubMed/NCBI View Article : Google Scholar

44 

Kono T, Kondo S, Pastore S, Shivji GM, Tomai MA, McKenzie RC and Sauder DN: Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression. Lymphokine Cytokine Res. 13:71–76. 1994.PubMed/NCBI

45 

Weber A, Zimmermann C, Mausberg AK, Kieseier BC, Hartung HP and Hofstetter HH: Induction of pro-inflammatory cytokine production in thymocytes by the immune response modifiers Imiquimod and Gardiquimod. Int Immunopharmacol. 17:427–431. 2013.PubMed/NCBI View Article : Google Scholar

46 

Wolf IH, Kodama K, Cerroni L and Kerl H: Nature of inflammatory infiltrate in superficial cutaneous malignancies during topical imiquimod treatment. Am J Dermatopathol. 29:237–241. 2007.PubMed/NCBI View Article : Google Scholar

47 

Wong JG, Toole JWP, Demers AA, Musto G and Wiseman MC: Topical 5% imiquimod in the treatment of lentigo maligna. J Cutan Med Surg. 16:245–249. 2012.PubMed/NCBI View Article : Google Scholar

48 

Schon M and Schon MP: The antitumoral mode of action of imiquimod and other imidazoquinolines. Curr Med Chem. 14:681–687. 2007.PubMed/NCBI View Article : Google Scholar

49 

Schon MP and Schon M: The small-molecule immune response modifier imiquimod-its mode of action and clinical use in the treatment of skin cancer. Expert Opin Ther Targets. 10:69–76. 2006.PubMed/NCBI View Article : Google Scholar

50 

Bilu D and Sauder DN: Imiquimod: Modes of action. Br J Dermatol. 149 (Suppl 66):5–8. 2003.PubMed/NCBI View Article : Google Scholar

51 

Levine E.N.a.V., Role of Topical Therapy: Imiquimod. 2017.

52 

Wagstaff AJ and Perry CM: Topical imiquimod: A review of its use in the management of anogenital warts, actinic keratoses, basal cell carcinoma and other skin lesions. Drugs. 67:2187–2210. 2007.PubMed/NCBI View Article : Google Scholar

53 

Megyeri K, Au WC, Rosztoczy I, Raj NB, Miller RL, Tomai MA and Pitha PM: Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. Mol Cell Biol. 15:2207–2218. 1995.PubMed/NCBI View Article : Google Scholar

54 

Sauder DN: Immunomodulatory and pharmacologic properties of imiquimod. J Am Acad Dermatol. 43:S6–S11. 2000.PubMed/NCBI View Article : Google Scholar

55 

Schon MP, Schon M and Klotz KN: The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion. J Invest Dermatol. 126:1338–1347. 2006.PubMed/NCBI View Article : Google Scholar

56 

Majewski S, Marczak M, Mlynarczyk B, Benninghoff B and Jablonska S: Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis. Int J Dermatol. 44:14–19. 2005.PubMed/NCBI View Article : Google Scholar

57 

Denning DP and Hirose T: Anti-tubulins DEPendably induce apoptosis. Nat Cell Biol. 16:741–743. 2014.PubMed/NCBI View Article : Google Scholar

58 

Schön MP and Schön M: Immune modulation and apoptosis induction: Two sides of the antitumoral activity of imiquimod. Apoptosis. 9:291–298. 2004.PubMed/NCBI View Article : Google Scholar

59 

Bong AB, Bonnekoh B, Franke I, Schön MP, Ulrich J and Gollnick H: Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology. 205:135–138. 2002.PubMed/NCBI View Article : Google Scholar

60 

Heikkinen AK and Susitaival P: Severe systemic reaction to topical imiquimod. Acta Derm Venereol. 91:594–595. 2011.PubMed/NCBI View Article : Google Scholar

61 

Cannon PS, O'Donnell B, Huilgol SC and Selva D: The ophthalmic side-effects of imiquimod therapy in the management of periocular skin lesions. Br J Ophthalmol. 95:1682–1685. 2011.PubMed/NCBI View Article : Google Scholar

62 

Benson E: Imiquimod: Potential risk of an immunostimulant. Australas J Dermatol. 45:123–124. 2004.PubMed/NCBI View Article : Google Scholar

63 

Somani N, Martinka M, Crawford RI, Dutz JP and Rivers JK: Treatment of atypical nevi with imiquimod 5% cream. Arch Dermatol. 143:379–385. 2007.PubMed/NCBI View Article : Google Scholar

64 

Hanna E, Abadi R and Abbas O: Imiquimod in dermatology: An overview. Int J Dermatol. 55:831–844. 2016.PubMed/NCBI View Article : Google Scholar

65 

Rosen T: Limited extent AIDS-related cutaneous Kaposi's sarcoma responsive to imiquimod 5% cream. Int J Dermatol. 45:854–856. 2006.PubMed/NCBI View Article : Google Scholar

66 

Ezzell TI, Fromowitz JS and Ramos-Caro FA: Recurrent pyogenic granuloma treated with topical imiquimod. J Am Acad Dermatol. 54 (5 Suppl):S244–S245. 2006.PubMed/NCBI View Article : Google Scholar

67 

Barba AR, Kapoor S and Berman B: An open label safety study of topical imiquimod 5% cream in the treatment of Molluscum contagiosum in children. Dermatol Online J. 7(20)2001.PubMed/NCBI

68 

Díaz-Guimaraens B, Saceda-Corralo D, Hermosa-Gelbard A, Moreno-Arrones ÓM, Dominguez-Santas M, Suarez-Valle A and Vañó-Galván S: Imiquimod-enhanced immunotherapy with diphencyprone for patients with alopecia areata. Dermatol Ther. 35(e15516)2022.PubMed/NCBI View Article : Google Scholar

69 

Palefsky JM, Lee JY, Jay N, Goldstone SE, Darragh TM, Dunlevy HA, Rosa-Cunha I, Arons A, Pugliese JC, Vena D, et al: Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med. 386:2273–2282. 2022.PubMed/NCBI View Article : Google Scholar

70 

Al Fayez N, Rouhollahi E, Ong CY, Wu J, Nguyen A, Böttger R, Cullis PR, Witzigmann D and Li SD: Hepatocyte-targeted delivery of imiquimod reduces hepatitis B virus surface antigen. J Control Release. 350:630–641. 2022.PubMed/NCBI View Article : Google Scholar

71 

Daude M, Dinulescu M, Nguyen JM, Maillard H, Duff FL, Machet L, Beylot-Barry M, Legoupil D, Wierzbicka-Hainaut E, Bedane C, et al: Efficacy of imiquimod in the management of lentigo maligna. J Eur Acad Dermatol Venereol. 27(10.1111/jdv.19141)2023.PubMed/NCBI View Article : Google Scholar

72 

Chang SH, Lin PY, Wu TK, Hsu CS, Huang SW, Li ZY, Liu KT, Kao JK, Chen YJ, Wong TW, et al: Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells. J Dermatol Sci. 107:142–150. 2022.PubMed/NCBI View Article : Google Scholar

73 

Urquhart JL and Weston WL: Treatment of multiple trichoepitheliomas with topical imiquimod and tretinoin. Pediatr Dermatol. 22:67–70. 2005.PubMed/NCBI View Article : Google Scholar

74 

Cantisani C, Lazic T, Richetta AG, Clerico R, Mattozzi C and Calvieri S: Imiquimod 5% cream use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov. 6:65–69. 2012.PubMed/NCBI View Article : Google Scholar

75 

Pasadyn SR and Cain R: Topical imiquimod induces severe weakness and myalgias after three applications: A case report. J Clin Aesthet Dermatol. 12:58–59. 2019.PubMed/NCBI

76 

Safadi MG, Hassan S, Patel V, Viglione M and Zahner SL: Imiquimod-induced hypertrophic lupus erythematosus-like reaction. Dermatol Online J. 28(10.5070/D328458526)2022.PubMed/NCBI View Article : Google Scholar

77 

Li HO, Aw M and Glassman SJ: Imiquimod-induced bullous pemphigoid: A case report. SAGE Open Med Case Rep. 11(2050313x231164222)2023.PubMed/NCBI View Article : Google Scholar

78 

Arias NM, Bonino CB, Feal PP, Rico MLP, Peñaranda JMS and Osorio IV: Lupus-like reaction following imiquimod treatment for actinic keratoses. Dermatol Ther. 35(e15700)2022.PubMed/NCBI View Article : Google Scholar

79 

Raman J, Bisbee E, Missall TA and Saikaly SK: A case of topical imiquimod induced fatigue. J Dermatolog Treat. 33:3202–3204. 2022.PubMed/NCBI View Article : Google Scholar

80 

McKinzie AH and Christman MA: Imiquimod-associated localized skin ulceration in a patient with uncontrolled diabetes. Obstet Gynecol. 140:316–319. 2022.PubMed/NCBI View Article : Google Scholar

81 

Martins P, Jesus J, Santos S, Raposo LR, Roma-Rodrigues C, Baptista PV and Fernandes AR: Heterocyclic anticancer compounds: Recent advances and the paradigm shift towards the use of nanomedicine's tool box. Molecules. 20:16852–16891. 2015.PubMed/NCBI View Article : Google Scholar

82 

Kumar S, Bawa S and Gupta H: Biological activities of quinoline derivatives. Mini Rev Med Chem. 9:1648–1654. 2009.PubMed/NCBI View Article : Google Scholar

83 

Chu XM, Wang C, Liu W, Liang LL, Gong KK, Zhao CY and Sun KL: Quinoline and quinolone dimers and their biological activities: An overview. Eur J Med Chem. 161:101–117. 2019.PubMed/NCBI View Article : Google Scholar

84 

Balderas-Renteria I, Gonzalez-Barranco P, Garcia A, Banik BK and Rivera G: Anticancer drug design using scaffolds of β-lactams, sulfonamides, quinoline, quinoxaline and natural products. Drugs advances in clinical trials. Curr Med Chem. 19:4377–4398. 2012.PubMed/NCBI View Article : Google Scholar

85 

Afzal O, Kumar S, Haider MR, Ali MR, Kumar R, Jaggi M and Bawa S: A review on anticancer potential of bioactive heterocycle quinoline. Eur J Med Chem. 97:871–910. 2015.PubMed/NCBI View Article : Google Scholar

86 

Bonilla-Ramirez L, Rios A, Quiliano M, Ramirez-Calderon G, Beltrán-Hortelano I, Franetich JF, Corcuera L, Bordessoulles M, Vettorazzi A, de Cerain AL, et al: Novel antimalarial chloroquine- and primaquine-quinoxaline 1,4-di-N-oxide hybrids: Design, synthesis, Plasmodium life cycle stage profile, and preliminary toxicity studies. Eur J Med Chem. 158:68–81. 2018.PubMed/NCBI View Article : Google Scholar

87 

Burguete A, Pontiki E, Hadjipavlou-Litina D, Ancizu S, Villar R, Solano B, Moreno E, Torres E, Pérez S, Aldana I and Monge A: Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents. Chem Biol Drug Des. 77:255–267. 2011.PubMed/NCBI View Article : Google Scholar

88 

Fabian L, Porro MT, Gómez N, Salvatori M, Turk G, Estrin D and Moglioni A: Design, synthesis and biological evaluation of quinoxaline compounds as anti-HIV agents targeting reverse transcriptase enzyme. Eur J Med Chem. 188(111987)2020.PubMed/NCBI View Article : Google Scholar

89 

El Newahie AMS, Nissan YM, Ismail NSM, El Ella DA, Khojah SM and Abouzid KAM: Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers. Molecules. 24(1175)2019.PubMed/NCBI View Article : Google Scholar

90 

Patinote C, Deleuze-Masquéfa C, Kaddour KH, Vincent LA, Larive R, Zghaib Z, Guichou JF, Assaf MD, Cuq P and Bonnet PA: Imidazo[1,2-a]quinoxalines for melanoma treatment with original mechanism of action. Eur J Med Chem. 212(113031)2021.PubMed/NCBI View Article : Google Scholar

91 

Lafaille F, Banaigs B, Inguimbert N, Enjalbal C, Doulain PE, Bonnet PA, Masquefa C and Bressolle FMM: Characterization of a new anticancer agent, EAPB0203, and its main metabolites: nuclear magnetic resonance and liquid chromatography-mass spectrometry studies. Anal Chem. 84:9865–9872. 2012.PubMed/NCBI View Article : Google Scholar

92 

Khier S, Deleuze-Masquéfa C, Moarbess G, Gattacceca F, Margout D, Solassol I, Cooper JF, Pinguet F, Bonnet PA and Bressolle FMM: Pharmacology of EAPB0203, a novel imidazo[1,2-a]quinoxaline derivative with anti-tumoral activity on melanoma. Eur J Pharm Sci. 39:23–29. 2010.PubMed/NCBI View Article : Google Scholar

93 

Morjaria S, Deleuze-Masquefa C, Lafont V, Gayraud S, Bompart J, Bonnet PA and Dornand J: Impairment of TNF-alpha production and action by imidazo[1,2- alpha] quinoxalines, a derivative family which displays potential anti-inflammatory properties. Int J Immunopathol Pharmacol. 19:525–538. 2006.PubMed/NCBI View Article : Google Scholar

94 

Lideikaitė A, Mozūraitienė J and Letautienė S: Analysis of prognostic factors for melanoma patients. Acta Med Litu. 24:25–34. 2017.PubMed/NCBI View Article : Google Scholar

95 

Drobits B, Holcmann M, Amberg N, Swiecki M, Grundtner R, Hammer M, Colonna M and Sibilia M: Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells. J Clin Invest. 122:575–585. 2012.PubMed/NCBI View Article : Google Scholar

96 

Chouchou A, Patinote C, Cuq P, Bonnet PA and Deleuze-Masquéfa C: Imidazo[1,2-a]quinoxalines derivatives grafted with amino acids: Synthesis and evaluation on A375 melanoma cells. Molecules. 23(2987)2018.PubMed/NCBI View Article : Google Scholar

97 

Quereux G and Dreno B: Fotemustine for the treatment of melanoma. Expert Opin Pharmacother. 12:2891–2904. 2011.PubMed/NCBI View Article : Google Scholar

98 

Hermine O, Ramos JC and Tobinai K: A review of new findings in adult T-cell leukemia-lymphoma: A focus on current and emerging treatment strategies. Adv Ther. 35:135–152. 2018.PubMed/NCBI View Article : Google Scholar

99 

Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, et al: Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: A proposal from an international consensus meeting. J Clin Oncol. 27:453–459. 2009.PubMed/NCBI View Article : Google Scholar

100 

Bazarbachi A, Suarez F, Fields P and Hermine O: How I treat adult T-cell leukemia/lymphoma. Blood. 118:1736–1745. 2011.PubMed/NCBI View Article : Google Scholar

101 

Cook LB, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, Horwitz S, Fields P, Tanase A, Bumbea H, et al: Revised adult T-cell leukemia-lymphoma international consensus meeting report. J Clin Oncol. 37:677–687. 2019.PubMed/NCBI View Article : Google Scholar

102 

Tsukasaki K, Marçais A, Nasr R, Kato K, Fukuda T, Hermine O and Bazarbachi A: Diagnostic approaches and established treatments for adult T cell leukemia lymphoma. Front Microbiol. 11(1207)2020.PubMed/NCBI View Article : Google Scholar

103 

El Hajj H, Tsukasaki K, Cheminant M, Bazarbachi A, Watanabe T and Hermine O: Novel treatments of adult T cell leukemia lymphoma. Front Microbiol. 11(1062)2020.PubMed/NCBI View Article : Google Scholar

104 

Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Löffler H, Hochhaus A and Heinze B: Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The german CML study group. Blood. 84:4064–4077. 1994.PubMed/NCBI

105 

Bisen A and Claxton DF: Tyrosine kinase targeted treatment of chronic myelogenous leukemia and other myeloproliferative neoplasms. Adv Exp Med Biol. 779:179–196. 2013.PubMed/NCBI View Article : Google Scholar

106 

Krause DS and Van Etten RA: Bedside to bench: Interfering with leukemic stem cells. Nat Med. 14:494–495. 2008.PubMed/NCBI View Article : Google Scholar

107 

Okimoto RA and Van Etten RA: Navigating the road toward optimal initial therapy for chronic myeloid leukemia. Curr Opin Hematol. 18:89–97. 2011.PubMed/NCBI View Article : Google Scholar

108 

Lagunas-Rangel FA, Chávez-Valencia V, Gómez-Guijosa MA and Cortes-Penagos C: Acute myeloid leukemia-genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res. 11:328–339. 2017.PubMed/NCBI

109 

Yilmaz M, Kantarjian H and Ravandi F: Acute promyelocytic leukemia current treatment algorithms. Blood Cancer J. 11(123)2021.PubMed/NCBI View Article : Google Scholar

110 

Borthakur G and Kantarjian H: Core binding factor acute myelogenous leukemia-2021 treatment algorithm. Blood Cancer J. 11(114)2021.PubMed/NCBI View Article : Google Scholar

111 

Molica M, Breccia M, Foa R, Jabbour E and Kadia TM: Maintenance therapy in AML: The past, the present and the future. Am J Hematol. 94:1254–1265. 2019.PubMed/NCBI View Article : Google Scholar

112 

Kassim AA and Savani BN: Hematopoietic stem cell transplantation for acute myeloid leukemia: A review. Hematol Oncol Stem Cell Ther. 10:245–251. 2017.PubMed/NCBI View Article : Google Scholar

113 

Lin WY, Fordham SE, Hungate E, Sunter NJ, Elstob C, Xu Y, Park C, Quante A, Strauch K, Gieger C, et al: Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. MedRxiv. 2021(2021.07.22.21259893)2021.PubMed/NCBI View Article : Google Scholar

114 

Falini B, Brunetti L, Sportoletti P and Martelli MP: NPM1-mutated acute myeloid leukemia: from bench to bedside. Blood. 136:1707–1721. 2020.PubMed/NCBI View Article : Google Scholar

115 

Wang AJ, Han Y, Jia N, Chen P and Minden MD: NPM1c impedes CTCF functions through cytoplasmic mislocalization in acute myeloid leukemia. Leukemia. 34:1278–1290. 2020.PubMed/NCBI View Article : Google Scholar

116 

Skayneh H, Jishi B, Hleihel R, Hamie M, El Hajj R, Deleuze-Masquefa C, Bonnet PA, El Sabban M and El Hajj H: EAPB0503, an imidazoquinoxaline derivative modulates SENP3/ARF mediated SUMOylation, and induces NPM1c degradation in NPM1 mutant AML. Int J Mol Sci. 23(3421)2022.PubMed/NCBI View Article : Google Scholar

117 

Sacks D and Noben-Trauth N: The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2:845–858. 2002.PubMed/NCBI View Article : Google Scholar

118 

Ley SV and Thomas AW: Modern synthetic methods for copper-mediated C(aryl)(bond)O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation. Angew Chem Int Ed Engl. 42:5400–5449. 2003.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
Copy and paste a formatted citation
Spandidos Publications style
Obeid J, Shaito A, El Hajj H, Deleuze‑masquefa C, Bonnet P, El‑Sabban M and Saliba J: Biological applications of imiquimod analogues: An update (Review). World Acad Sci J 5: 20, 2023.
APA
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., & Saliba, J. (2023). Biological applications of imiquimod analogues: An update (Review). World Academy of Sciences Journal, 5, 20. https://doi.org/10.3892/wasj.2023.197
MLA
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., Saliba, J."Biological applications of imiquimod analogues: An update (Review)". World Academy of Sciences Journal 5.3 (2023): 20.
Chicago
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., Saliba, J."Biological applications of imiquimod analogues: An update (Review)". World Academy of Sciences Journal 5, no. 3 (2023): 20. https://doi.org/10.3892/wasj.2023.197
Copy and paste a formatted citation
x
Spandidos Publications style
Obeid J, Shaito A, El Hajj H, Deleuze‑masquefa C, Bonnet P, El‑Sabban M and Saliba J: Biological applications of imiquimod analogues: An update (Review). World Acad Sci J 5: 20, 2023.
APA
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., & Saliba, J. (2023). Biological applications of imiquimod analogues: An update (Review). World Academy of Sciences Journal, 5, 20. https://doi.org/10.3892/wasj.2023.197
MLA
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., Saliba, J."Biological applications of imiquimod analogues: An update (Review)". World Academy of Sciences Journal 5.3 (2023): 20.
Chicago
Obeid, J., Shaito, A., El Hajj, H., Deleuze‑masquefa, C., Bonnet, P., El‑Sabban, M., Saliba, J."Biological applications of imiquimod analogues: An update (Review)". World Academy of Sciences Journal 5, no. 3 (2023): 20. https://doi.org/10.3892/wasj.2023.197
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team