Sole supplier: Deforolimus, 572924-54-0

Description: Ridaforolimus, also known as AP23573, MK-8669 Deforolimus, is an investigational targeted and small-molecule inhibitor of the protein mTOR, a protein that acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins, such as PI3K, AKT and PTEN known to be important to malignancy. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis. It has had promising results in a clinical trial for advanced soft tissue and bone sarcoma.   

Name: Ridaforolimus
CAS#: 572924-54-0
Chemical Formula: C53H84NO14P
Exact Mass: 989.56294
Molecular Weight: 990.21
Elemental Analysis: C, 64.29; H, 8.55; N, 1.41; O, 22.62; P, 3.13

Synonym: AP23573; AP 23573; AP-23573; MK8669; MK 8669; MK-8669; Deforolimus, Ridaforolimus

IUPAC/Chemical Name: (1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28Z,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl dimethylphosphinate

SMILES Code: O=P(C)(C)O[C@H]1[C@H](OC)C[C@H](C[C@H]([C@H](CC([C@H](C)/C=C(C)/[C@@H](O)[C@H]2OC)=O)OC([C@]3([H])CCCCN3C(C([C@@](O4)(O)[C@H](C)CC[C@@]4([H])C[C@H](OC)/C(C)=C\C=C\C=C\[C@@H](C)C[C@@H](C)C2=O)=O)=O)=O)C)CC1

 1: Blay JY. Updating progress in sarcoma therapy with mTOR inhibitors. Ann Oncol. 2010 Jun 29. [Epub ahead of print] PubMed PMID: 20591820.

2: Penel N, Watelle F, Vanhuyse M, Adenis A. [Treatment of adult patients with metastatic sarcoma: current shift in concepts]. Bull Cancer. 2010 Jun 1;97(6):687-91. French. PubMed PMID: 20462829.

3: Rodriguez-Pascual J, Cheng E, Maroto P, Duran I. Emergent toxicities associated with the use of mTOR inhibitors in patients with advanced renal carcinoma. Anticancer Drugs. 2010 Jun;21(5):478-86. Review. PubMed PMID: 20401967.

4: Dancey J. mTOR signaling and drug development in cancer. Nat Rev Clin Oncol. 2010 Apr;7(4):209-19. Epub 2010 Mar 16. PubMed PMID: 20234352.

5: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Nov;31(9):597-633. PubMed PMID: 20094643.

6: Gibbons JJ, Abraham RT, Yu K. Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol. 2009 Dec;36 Suppl 3:S3-S17. Review. PubMed PMID: 19963098.

7: Sessa C, Tosi D, Viganò L, Albanell J, Hess D, Maur M, Cresta S, Locatelli A, Angst R, Rojo F, Coceani N, Rivera VM, Berk L, Haluska F, Gianni L. Phase Ib study of weekly mammalian target of rapamycin inhibitor ridaforolimus (AP23573; MK-8669) with weekly paclitaxel. Ann Oncol. 2010 Jun;21(6):1315-22. Epub 2009 Nov 9. PubMed PMID: 19901013.

8: Sonis S, Treister N, Chawla S, Demetri G, Haluska F. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients. Cancer. 2010 Jan 1;116(1):210-5. PubMed PMID: 19862817.

9: Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2009 Oct 27;2:45. Review. PubMed PMID: 19860903; PubMed Central PMCID: PMC2775749.

10: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jul-Aug;31(6):397-417. PubMed PMID: 19798455.

11: Coiffier B, Ribrag V. Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle cell lymphoma and other hematologic malignancies. Leuk Lymphoma. 2009 Dec;50(12):1916-30. Review. PubMed PMID: 19757306.

12: Hersey P, Bastholt L, Chiarion-Sileni V, Cinat G, Dummer R, Eggermont AM, Espinosa E, Hauschild A, Quirt I, Robert C, Schadendorf D. Small molecules and targeted therapies in distant metastatic disease. Ann Oncol. 2009 Aug;20 Suppl 6:vi35-40. Review. PubMed PMID: 19617296; PubMed Central PMCID: PMC2712592.

13: Kapoor A, Figlin RA. Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma. Cancer. 2009 Aug 15;115(16):3618-30. Review. PubMed PMID: 19479976.

14: Konings IR, Verweij J, Wiemer EA, Sleijfer S. The applicability of mTOR inhibition in solid tumors. Curr Cancer Drug Targets. 2009 May;9(3):439-50. Review. PubMed PMID: 19442061.

15: Guertin DA, Sabatini DM. The pharmacology of mTOR inhibition. Sci Signal. 2009 Apr 21;2(67):pe24. PubMed PMID: 19383975.

16: Mahalingam D, Sankhala K, Mita A, Giles FJ, Mita MM. Targeting the mTOR pathway using deforolimus in cancer therapy. Future Oncol. 2009 Apr;5(3):291-303. Review. PubMed PMID: 19374536.

17: Dreyer C, Raymond E, Faivre S. [Targeted therapies and their indications in solid neoplasias]. Rev Med Interne. 2009 May;30(5):416-24. Epub 2009 Mar 18. Review. French. PubMed PMID: 19299048.

18: Hartford CM, Desai AA, Janisch L, Karrison T, Rivera VM, Berk L, Loewy JW, Kindler H, Stadler WM, Knowles HL, Bedrosian C, Ratain MJ. A phase I trial to determine the safety, tolerability, and maximum tolerated dose of deforolimus in patients with advanced malignancies. Clin Cancer Res. 2009 Feb 15;15(4):1428-34. PubMed PMID: 19228743.

19: Dreyer C, Sablin MP, Faivre S, Raymond E. [Topics in mTOR pathway and its inhibitors]. Bull Cancer. 2009 Jan;96(1):87-94. Review. French. PubMed PMID: 19211363.

20: Mita M, Sankhala K, Abdel-Karim I, Mita A, Giles F. Deforolimus (AP23573) a novel mTOR inhibitor in clinical development. Expert Opin Investig Drugs. 2008 Dec;17(12):1947-54. Review. PubMed PMID: 19012509.

21: Figlin RA, Brown E, Armstrong AJ, Akerley W, Benson AB 3rd, Burstein HJ, Ettinger DS, Febbo PG, Fury MG, Hudes GR, Kies MS, Kwak EL, Morgan RJ Jr, Mortimer J, Reckamp K, Venook AP, Worden F, Yen Y. NCCN Task Force Report: mTOR inhibition in solid tumors. J Natl Compr Canc Netw. 2008 Sep;6 Suppl 5:S1-S20; quiz S21-S22. Review. PubMed PMID: 18926092.

22: Fasolo A, Sessa C. mTOR inhibitors in the treatment of cancer. Expert Opin Investig Drugs. 2008 Nov;17(11):1717-34. Review. PubMed PMID: 18922108.

23: Tomillero A, Moral MA. Gateways to clinical trials. July-August 2008. Methods Find Exp Clin Pharmacol. 2008 Jul-Aug;30(6):459-95. PubMed PMID: 18850047.

24: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 May;30(4):313-31. PubMed PMID: 18773127.

25: Abdel-Karim IA, Giles FJ. Mammalian target of rapamycin as a target in hematological malignancies. Curr Probl Cancer. 2008 Jul-Aug;32(4):161-77. Review. PubMed PMID: 18655914.

26: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Apr;30(3):231-51. PubMed PMID: 18597009.

27: Gadducci A, Tana R, Cosio S, Fanucchi A, Genazzani AR. Molecular target therapies in endometrial cancer: from the basic research to the clinic. Gynecol Endocrinol. 2008 May;24(5):239-49. Review. PubMed PMID: 18569027.

28: Smith SM. Clinical development of mTOR inhibitors: a focus on lymphoma. Rev Recent Clin Trials. 2007 May;2(2):103-10. Review. PubMed PMID: 18473994.

29: Rizzieri DA, Feldman E, Dipersio JF, Gabrail N, Stock W, Strair R, Rivera VM, Albitar M, Bedrosian CL, Giles FJ. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008 May 1;14(9):2756-62. PubMed PMID: 18451242.

30: Wilkes GM. Drug essentials mTOR inhibitors. Oncology (Williston Park). 2008 Apr;22(4 Suppl Nurse Ed):43-4. PubMed PMID: 19856563.

31: Gridelli C, Maione P, Rossi A. The potential role of mTOR inhibitors in non-small cell lung cancer. Oncologist. 2008 Feb;13(2):139-47. Review. PubMed PMID: 18305058.

32: Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, Patnaik A, Mathews L, Ricart AD, Mays T, Knowles H, Rivera VM, Kreisberg J, Bedrosian CL, Tolcher AW. Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol. 2008 Jan 20;26(3):361-7. PubMed PMID: 18202410.

33: Cohen EE. mTOR: the mammalian target of replication. J Clin Oncol. 2008 Jan 20;26(3):348-9. PubMed PMID: 18202406.

34: Iwenofu OH, Lackman RD, Staddon AP, Goodwin DG, Haupt HM, Brooks JS. Phospho-S6 ribosomal protein: a potential new predictive sarcoma marker for targeted mTOR therapy. Mod Pathol. 2008 Mar;21(3):231-7. Epub 2007 Dec 21. PubMed PMID: 18157089.

35: Huang JJ, Lin TY. [mTOR signal pathway and its inhibitors in antitumor therapy: a review]. Ai Zheng. 2007 Dec;26(12):1397-403. Review. Chinese. PubMed PMID: 18076811.

36: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Oct;29(8):547-83. PubMed PMID: 18040531.

37: MacKenzie AR, von Mehren M. Mechanisms of mammalian target of rapamycin inhibition in sarcoma: present and future. Expert Rev Anticancer Ther. 2007 Aug;7(8):1145-54. Review. PubMed PMID: 18028023.

38: Wan X, Helman LJ. The biology behind mTOR inhibition in sarcoma. Oncologist. 2007 Aug;12(8):1007-18. Review. PubMed PMID: 17766661.

39: Mita MM, Tolcher AW. The role of mTOR inhibitors for treatment of sarcomas. Curr Oncol Rep. 2007 Jul;9(4):316-22. Review. PubMed PMID: 17588357.

40: von Mehren M. New therapeutics for soft-tissue sarcomas in adults. Oncology (Williston Park). 2007 Jan;21(1):123-6. PubMed PMID: 17313160.

41: Elit L. Drug evaluation: AP-23573--an mTOR inhibitor for the treatment of cancer. IDrugs. 2006 Sep;9(9):636-44. PubMed PMID: 16952072.

42: Smolewski P. Recent developments in targeting the mammalian target of rapamycin (mTOR) kinase pathway. Anticancer Drugs. 2006 Jun;17(5):487-94. Review. PubMed PMID: 16702804.