Temsirolimus

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Temsirolimus is an ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors. Temsirolimus (CCI-779) is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007.

Price and Availability

Temsirolimus, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 202870Name: TemsirolimusCAS#: 162635-04-3Chemical Formula: C56H87NO16Exact Mass: 1029.60249Molecular Weight: 1030.29Elemental Analysis:C, 65.28; H, 8.51; N, 1.36; O, 24.85

Synonym:CCI779; CCI-779; CCI 779; Temsirolimus; US brand name: Torisel.

IUPAC/Chemical Name:(1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate.

InChi Key:CBPNZQVSJQDFBE-FUXHJELOSA-N

InChi Code:InChI=1S/C56H87NO16/c1-33-17-13-12-14-18-34(2)45(68-9)29-41-22-20-39(7)56(67,73-41)51(63)52(64)57-24-16-15-19-42(57)53(65)71-46(30-43(60)35(3)26-38(6)49(62)50(70-11)48(61)37(5)25-33)36(4)27-40-21-23-44(47(28-40)69-10)72-54(66)55(8,31-58)32-59/h12-14,17-18,26,33,35-37,39-42,44-47,49-50,58-59,62,67H,15-16,19-25,27-32H2,1-11H3/b14-12+,17-13+,34-18+,38-26+/t33-,35-,36-,37-,39-,40+,41+,42+,44-,45+,46+,47-,49-,50+,56-/m1/s1

SMILES Code:O=C(O[C@H]1[C@H](OC)C[C@H](C[C@H]([C@@H](OC([C@@](CCCC2)([H])N2C(C([C@@]3(O)[C@H](C)CC[C@@](O3)([H])C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@H](O)/C(C)=C/[C@H]4C)=O)=O)=O)=O)CC4=O)C)CC1)C(C)(CO)CO

Technical Data

Additional Information

Temsirolimus (CCI-779) is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel. mTOR (mammalian target of rapamycin) is a kinase enzyme inside the cell that collects and interprets the numerous and varied growth and survival signals received by tumor cells. When the kinase activity of mTOR is activated, its downstream effectors, the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a) are increased. HIF-1a then stimulates VEGF. Whether or not mTOR kinase is activated, determines whether the tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis. mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes. These activating factors are known to be important for malignant transformation and progression. mTOR is particularly important in the biology of renal cancer (RCC) owing to its function in regulating HIF-1a levels. Mutation or loss of the von Hippel Lindau tumor-suppressor gene is common in RCC and is manifested by reduced degradation of HIF-1a. In RCC tumors, activated mTOR further exacerbates accumulation of HIF-1a by increasing synthesis of this transcription factor and its angiogenic target gene products. Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells. Treatment with temsirolimus leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF.    

References

 1: Gomez-Fernandez C, Garden BC, Wu S,Feldman DR, Lacouture ME. The risk of skin rash and stomatitis with themammalian target of rapamycin inhibitor temsirolimus: a systematicreview of the literature and meta-analysis. Eur J Cancer. 2012Feb;48(3):340-6. Epub 2011 Dec 27. Review. PubMed PMID: 22206873.

2: De Masson A, Fouchard N, Méry-Bossard L, Dauendorffer JN. Cutaneousand mucosal aphthosis during temsirolimus therapy for advanced renalcell carcinoma: review of cutaneous and mucosal side effects of mTORinhibitors. Dermatology. 2011;223(1):4-8. Epub 2011 Aug 16. Review.PubMed PMID: 21846963.

3: Hess G. Temsirolimus for the treatment of mantle cell lymphoma.Expert Rev Hematol. 2009 Dec;2(6):631-40. Review. PubMed PMID: 21082954.

4: Gerullis H, Ecke TH, Eimer C, Heuck CJ, Otto T. mTOR-inhibition inmetastatic renal cell carcinoma. Focus on temsirolimus: a review.Minerva Urol Nefrol. 2010 Dec;62(4):411-23. Review. PubMed PMID:20944541.

5: Hoy SM, McKeage K. Temsirolimus: In relapsed and/or refractory mantlecell lymphoma. Drugs. 2010 Oct 1;70(14):1819-29. doi:10.2165/11204940-000000000-00000. Review. PubMed PMID: 20836575.

6: Norum J, Nieder C, Kondo M. Sunitinib, sorafenib, temsirolimus orbevacizumab in the treatment of metastatic renal cell carcinoma: areview of health economic evaluations. J Chemother. 2010Apr;22(2):75-82. Review. PubMed PMID: 20435564.

7: Ravaud A, Bernhard JC, Gross-Goupil M, Digue L, Ferriere JM. [mTORinhibitors: temsirolimus and everolimus in the treatment of renal cellcarcinoma]. Bull Cancer. 2010;97:45-51. Review. French. PubMed PMID:20418203.

8: Stock C, Zaccagnini M, Schulze M, Teber D, Rassweiler JJ.Temsirolimus. Recent Results Cancer Res. 2010;184:189-97. Review. PubMedPMID: 20072839.

9: Dancey JE, Curiel R, Purvis J. Evaluating temsirolimus activity inmultiple tumors: a review of clinical trials. Semin Oncol. 2009 Dec;36Suppl 3:S46-58. Review. PubMed PMID: 19963100.

10: Hess G, Smith SM, Berkenblit A, Coiffier B. Temsirolimus in mantlecell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Oncol. 2009Dec;36 Suppl 3:S37-45. Review. PubMed PMID: 19963099.