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vopimetostat + RAS(ON) inhibitors
- Development stage
- Unknown
- Lead developer
- Tango Therapeutics
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Vopimetostat + RAS(ON) inhibitors is an investigational combination therapy being developed through a partnership between Tango Therapeutics and Revolution Medicines. The regimen consists of vopimetostat (TNG462), an oral, once-daily, MTA-cooperative PRMT5 (protein arginine methyltransferase 5) inhibitor, combined with a RAS(ON) inhibitor—either daraxonrasib (RMC-6236), a multi-selective RAS(ON) inhibitor, or zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor. Vopimetostat selectively targets cancer cells harboring MTAP (methylthioadenosine phosphorylase) deletion by binding to the MTA-PRMT5 complex, inducing synthetic lethality. The RAS(ON) inhibitors target the active, GTP-bound state of oncogenic RAS proteins. This combination is primarily being evaluated in Phase 1/2 clinical trials (NCT06922591) for the treatment of MTAP-deleted, RAS-mutant cancers, including metastatic pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC).
- Other names
- vopimetostat + daraxonrasibvopimetostat + zoldonrasib
02
Targets
PRMT5 (Protein arginine N-methyltransferase 5)HRAS (H-Ras protein)PPIA (Peptidyl-prolyl cis-trans isomerase A)
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