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Synonyms: CCI-779 | Torisel®
temsirolimus is an approved drug (FDA & EMA (2007))
Compound class:
Synthetic organic
Comment: Temsirolimus is a Type-3 kinase inhibitor and was first approved by the FDA in 2007. There is some ambiguity in the literature surrounding the exact stereochemistry of temsirolimus. Other common representations are CID 23724530, CID 24847874 and CID 9876533. Our representation and the PubChem and ChEMBL links in the table above show a structure identical to that contained in the INN record for this drug.
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖
View more information in the IUPHAR Pharmacology Education Project: temsirolimus |
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| No information available. |
Summary of Clinical Use  |
| Used in the treatment of renal cell carcinomas. |
| Mechanism Of Action and Pharmacodynamic Effects |
| Temsirolimus is a mTOR (controls cell division) kinase inhibitor that binds with high affinity to FK506 binding protein-12 (FKBP-12), thereby forming a drug/protein complex that inhibits the activation of mTOR, but at high concentrations (10-20 µM) can inhibit mTOR without binding FKBP-12. Inhibition of mTOR activity results in G1 growth arrest, and combined with concomittant reduction in levels of hypoxia-inducible factors HIF-1&alpha and HIF-2α and VEGF, results in a reduction in cell proliferation, angiogenesis, and glucose uptake and apoptosis. |
| Pharmacokinetics |
| Absorption/Distribution |
| Temsirolimus is administered as an intravenous infusion over 30-60 minutes and peak concentration is typically observed by the end of the infusion. Distribution is partitioned into formed blood elements, accounted for by the drug binding to FKBP-12 in blood cells. |
| Biotransformation/Metabolism |
| Temsirolimus is metabolized primarily in the liver by CYP3A4, generating sirolimus, the principal active metabolite found following IV treatment. It is recommended that the dose of everolimus should be reduced if a known CYP3A4 inhibitor is coadministered, or be increased if a CYP3A4 activator is coadministered. |
| Elimination |
| Temsirolimus is predominantly excreted in feces (76%) with 4.6% of drug and metabolites recovered in urine. 17% of drug was not recovered by either route following a 14-day sample collection. |
| Population pharmacokinetics |
| Temsirolimus and sirolimus pharmacokinetics are not significantly affected by age, gender or ethnicity in tested populations. In the pediatric population net exposure as measured by the sum of temsirolimus and sirolimus AUCs (AUCsum) was comparable to that for adults. |
| Organ function impairment |
| Since temsirolimus is cleared predominantly by the liver caution should be used when treating patients with hepatic impairment. |
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
