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temsirolimus + gemcitabine
- Development stage
- Discontinued
- Lead developer
- Pfizer
- Modality
- Small Molecules
- Administration
- Intravenous
01
Overview
Temsirolimus + gemcitabine is a combination therapy regimen consisting of the mTOR inhibitor temsirolimus and the antimetabolite gemcitabine. Temsirolimus, a derivative of sirolimus, binds to the intracellular protein FKBP-12, and the resulting complex inhibits the activity of mTOR Complex 1 (mTORC1), thereby blocking downstream signaling pathways essential for cell cycle progression and angiogenesis. Gemcitabine is a nucleoside analog that is phosphorylated intracellularly into active metabolites; these metabolites inhibit DNA synthesis by competing with deoxycytidine triphosphate for incorporation into DNA and by inhibiting ribonucleotide reductase, leading to a depletion of deoxynucleotide pools. This combination was specifically investigated in a Phase 1 dose-escalation trial led by Massachusetts General Hospital for the treatment of previously untreated metastatic pancreatic adenocarcinoma.
- Other names
- temsirolimus and gemcitabine combination
02
Targets
DNARNR (Ribonucleotide reductase)mTOR (Mammalian target of rapamycin kinase)
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