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Drug intelligence / Profile preview
RMC-9805 + RMC-6236 + 5-fluorouracil
- Development stage
- Unknown
- Lead developer
- REVOLUTION Medicines
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
A **combination therapy** being investigated primarily for cancers harboring KRAS G12D mutations. **RMC-9805** is a selective, oral, covalent inhibitor that targets the active, GTP-bound state of KRAS G12D mutant proteins (a RAS(ON) inhibitor). **RMC-6236** is a multi-selective pan-RAS(ON) inhibitor that targets multiple active RAS isoforms. **5-fluorouracil** is a well-established cytotoxic antimetabolite that inhibits thymidylate synthase, disrupting DNA and RNA synthesis. The rationale for this combination is to enhance the antitumor effect by simultaneously inhibiting oncogenic signaling (KRAS) and DNA synthesis, with ongoing early-phase trials in KRAS G12D-mutant solid tumors, including pancreatic and non-small cell lung cancer.
- Other names
- fluorouracil
02
Targets
KRASG12D (Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutant)NRAS (Neuroblastoma RAS viral oncogene homolog)TS (Thymidylate synthase)HRAS (H-Ras protein)
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