Temsirolimus

• Catalog No.: DB06287
• CAS Number: 162635-04-3
• M. F.: C56H87NO16
• M. W.: 1030.28708

SYNONYMS

• IUPAC name: (1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,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[30.3.1.0^{4,9}]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
• IUPAC Traditional name: torisel
• Brand Name: Torisel
• Synonyms: CCI-779; temsirolimus

DATABASE IDS

• PubChem SID: 99443243
• CAS Number: 162635-04-3
• PubChem CID: 23724530

DETAILS

Description (English)

• Drug Groups: approved; investigational
• Description: Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the 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.
• Indication: For the treatment of renal cell carcinoma (RCC). Also investigated for use/treatment in breast cancer, lymphoma (unspecified), rheumatoid arthritis, and multiple myeloma.
• Toxicity: Temsirolimus has been administered to patients with cancer in phase 1 and 2 trials with repeated intravenous doses as high as 220 mg/m2. The risk of several serious adverse events, including thrombosis, bowel perforation, interstitial lung disease (ILD), seizure, and psychosis, is increased with doses of temsirolimus greater than 25 mg.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily metabolized by cytochrome P450 3A4 in the human liver. Sirolimus, an equally potent metabolite, is the primary metabolite in humans following IV infusion. Other metabolic pathways observed in in vitro temsirolimus metabolism studies include hydroxylation, reduction and demethylation.
• Absorption: Infused intravenous over 30 - 60 minutes. C_max is typically observed at the end of infusion
• Half Life: Temsirolimus exhibits a bi-exponential decline in whole blood concentrations and the mean half-lives of temsirolimus and sirolimus were 17.3 hr and 54.6 hr, respectively.
• Protein Binding: 87% bound to plasma proteins in vitro at a concentration of 100 ng/ml
• Elimination: Excreted predominantly in feces (76%), 4.6% of drug and metabolites recovered in urine. 17% of drug was not recovered by either route following a 14-day sample collection.
• Distribution: 172 L in whole blood of cancer patients; both temsirolimus and sirolimus are extensive distributed partitioned into formed blood elements
• Clearance: 16.2 L/h (22%)
• References: Wyeth Pharmaceuticals Inc. Torisel? (temsirolimus) injection prescribing information. Philadelphia, PA: 2010 Sep.; Boni J, Leister C, Burns J, Cincotta M, Hug B, Moore L: Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome p450-inducing medications. J Clin Pharmacol. 2007 Nov;47(11):1430-9. Epub 2007 Oct 3. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Wyeth Pharmaceuticals Inc. Torisel? (temsirolimus) injection prescribing information. Philadelphia, PA: 2010 Sep.
• Boni J, Leister C, Burns J, Cincotta M, Hug B, Moore L: Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome p450-inducing medications. J Clin Pharmacol. 2007 Nov;47(11):1430-9. Epub 2007 Oct 3. Pubmed