RAS (pan-RAS, RAS-mutant tumors)

Class

Non-degrading molecular glue RAS inhibitor

Pathway

Modulates RAS GTPase protein-protein interactions in RAS-mutant cancers

RAS is a family of small proteins that act as molecular switches inside cells, cycling between an inactive, GDP-bound state and an active, GTP-bound state that transmits growth and survival signals through the MAPK and PI3K pathways. Mutations in RAS genes, common across many solid tumors, lock the protein in its active conformation, producing continuous pro-growth signaling independent of upstream cues. Because RAS proteins have a smooth surface with few pockets suitable for conventional drug binding, and because they bind GTP with very high affinity, they were historically considered difficult therapeutic targets. Molecular glue inhibitors represent a newer strategy: rather than occupying an existing pocket, they induce or stabilize a novel interface between RAS and another cellular protein, creating a composite surface that blocks RAS from engaging its downstream signaling partners. A pan-RAS approach, active across multiple RAS mutations and isoforms rather than one specific variant, aims to address the genetic diversity of RAS-mutant cancers and the possibility that tumors carry or evolve different mutant forms. This mechanism is broadly relevant to cancers driven by RAS pathway activation, where suppressing this signaling node can restrain tumor proliferation and survival.