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vorinostat + pemetrexed + cisplatin
- Development stage
- Phase 2
- Lead developer
- Merck
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Vorinostat + pemetrexed + cisplatin is a combination regimen of three chemotherapeutic agents used in clinical trials for advanced solid tumors, including non-small cell lung cancer and malignant pleural mesothelioma. Vorinostat is a histone deacetylase (HDAC) inhibitor that induces cell cycle arrest and apoptosis by inhibiting HDAC1, HDAC2, HDAC3, and HDAC6. Pemetrexed is an antifolate antineoplastic agent that disrupts folate-dependent metabolic processes essential for cell replication by inhibiting several enzymes involved in purine and pyrimidine synthesis. Cisplatin is a platinum-based chemotherapy drug that forms DNA crosslinks leading to apoptosis. The combination aims to enhance antitumor activity through complementary mechanisms: epigenetic modulation (vorinostat), inhibition of nucleotide synthesis (pemetrexed), and direct DNA damage (cisplatin). This regimen has been evaluated in phase I/II studies for safety and efficacy in patients with advanced or refractory solid tumors[2][3][8].
- Other names
- suberoylanilide hydroxamic acidLY231514LY-231514LY 231514cis-diamminedichloroplatinum(II)
02
Targets
DNADHFR (Dihydrofolate reductase)GART (GAR transformylase)HDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)HDAC6 (Histone deacetylase 6)TS (Thymidylate synthase)
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