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carboplatin + ganetespib + pemetrexed
- Development stage
- Phase 2
- Lead developer
- Madrigal Pharmaceuticals
- Modality
- Small Molecules
- Administration
- Intravenous
01
Overview
A combination therapy consisting of carboplatin, ganetespib, and pemetrexed. Ganetespib is a potent small-molecule Heat shock protein 90 (Hsp90) inhibitor that destabilizes several Hsp90 client proteins involved in DNA repair and cell cycle regulation. When combined with carboplatin (which forms DNA interstrand crosslinks) and pemetrexed (an antifolate), this regimen shows synergistic antitumor effects by preventing DNA repair, abrogating cell cycle checkpoints, and inducing massive chromosome fragmentation followed by cell death. This combination has been primarily studied for the treatment of malignant pleural mesothelioma.
02
Targets
DNADHFR (Dihydrofolate reductase)GART (GAR transformylase)HSP90 (Heat shock protein 90 chaperone complex)TS (Thymidylate synthase)HSP90AA1 (Heat shock protein HSP90-alpha)
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