QuickView for Temsirolimus (compound)

Summary
General Info

PubChem

PubChem Compound 5469176

Name:	temsirolimus
PubChem Compound ID:	5469176
Molecular formula:	C₅₆H₈₇NO₁₆
Molecular weight:	1030.29 g/mol
Synonyms:	NSC683864

DrugBank

Identification

Name:	temsirolimus
Name (isomeric):	DB06287
Drug Type:	small molecule
Synonyms:	CCI-779
Brand:	Torisel
Category:	Antineoplastic Agents, Protein Kinase Inhibitors
CAS number:	162635-04-3

Pharmacology

Indication:	For the treatment of renal cell carcinoma (RCC). Also investigated for use/treatment in breast cancer, lymphoma (unspecified), rheumatoid arthritis, and multiple myeloma.
Mechanism of Action:	Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphoryla... show more » Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor. show less «
Absorption:	Infused intravenous over 30 - 60 minutes. C_max is typically observed at the end of infusion
Protein binding:	87% bound to plasma proteins in vitro at a concentration of 100 ng/ml
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.
Route of 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.
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.
Clearance:	16.2 L/h (22%)
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

Interactions

Drug interaction:

Tipranavir	Tipranavir may affect the efficacy/toxicity of Temsirolimus.
Nefazodone	Nefazodone may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Ritonavir	Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Rifampin	Rifampin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Phenobarbital	Phenobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Tipranavir	Tipranavir may affect the efficacy/toxicity of Temsirolimus.
Nefazodone	Nefazodone may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Ritonavir	Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Rifampin	Rifampin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Phenobarbital	Phenobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Nevirapine	Nevirapine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Indinavir	Indinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Phenytoin	Phenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Atazanavir	Atazanavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Saquinavir	Saquinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Rifapentine	Rifapentine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Primidone	Primidone may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Lopinavir	Lopinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Telithromycin	Telithromycin may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Dexamethasone	Dexamethasone may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Natalizumab	Temsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.
Nicardipine	Nicardipine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Miconazole	Miconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Fosphenytoin	Fosphenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Carbamazepine	Carbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Fluorouracil	Co-administration of Temsirolimus and Fluorouracil may result in serious adverse drug reactions.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of temsirolimus and its active metabolite, sirolimus, by decreasing their metabolism. Concomitant therapy should be avoided.
Aminoglutethimide	Aminoglutethimide may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Bosentan	Bosentan may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Isoniazid	Isoniazid may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Sunitinib	Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.
Rifabutin	Rifabutin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Tacrolimus	Temsirolimus may decrease the blood concentration of Tacrolimus. Concomitant therapy may increase the adverse/toxic effects of both agents. Concomitant therapy should be avoided.
Pentobarbital	Pentobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trandolapril	Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
Gemcitabine	Co-administration of Temsirolimus and Gemcitabine may result in serious adverse drug reactions.
St. John's Wort	St. John's Wort may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Fosamprenavir	Fosamprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Posaconazole	Posaconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Nelfinavir	Nelfinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Clarithromycin	Clarithromycin may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Itraconazole	Itraconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Nafcillin	Nafcillin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Imatinib	Imatinib may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Ketoconazole	Ketoconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Oxcarbazepine	Oxcarbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Quinidine	Quinidine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Amprenavir	Amprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Efavirenz	Efavirenz may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Delavirdine	Delavirdine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Darunavir	Darunavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
Conivaptan	Conivaptan may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

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Targets

Serine/threonine-protein kinase mTOR

Enzymes

Transporters

Multidrug resistance protein 1