Zoldonrasib — Investigational Agent
KRAS Inhibitor · Phase 1 · Revolution Medicines, Inc.
Mechanism of Action
Zoldonrasib is an oral, covalent, RAS(ON) G12D-selective tri-complex inhibitor. It binds cyclophilin A to form a tri-complex that covalently and selectively engages the active GTP-bound (ON) state of KRAS G12D, blocking effector engagement and downstream RAS-MAPK signaling. This is a distinct approach from the reversible non-covalent G12D inhibitor MRTX1133, and it is selective for G12D over wild-type KRAS and other RAS mutants.
Investigational Indications
- KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC)
- KRAS G12D-mutant non-small cell lung cancer (NSCLC)
- KRAS G12D-mutant colorectal cancer (CRC)
- Other KRAS G12D-mutant advanced solid tumors