01 · The pathway
KRAS is a molecular switch in the RAS signaling network.
KRAS is one of three canonical RAS genes alongside NRAS and HRAS. RAS proteins cycle between an inactive GDP-bound state and an active GTP-bound state. In the active state, they engage effector proteins that propagate signals controlling cell growth and survival.
Oncogenic RAS mutations can bias this switch toward persistent activation. That sustained signaling is a central driver in several tumor types and is especially common in pancreatic ductal adenocarcinoma (PDAC).
02 · Active and inactive states
RAS(ON) and RAS(OFF) describe state—not separate proteins.
RAS(OFF)
The relatively inactive state. Some earlier mutation-selective inhibitors bind this state.
RAS(ON)
The active signaling state. Daraxonrasib is described as a RAS(ON) multi-selective inhibitor.
“Multi-selective” reflects activity against more than one RAS variant rather than a single mutation alone. The 2024 translational paper describes engagement of mutant and wild-type canonical RAS in the active state.
Read the Cancer Discovery paper↗03 · Pancreatic cancer context
PDAC is one of the clearest disease settings for RAS biology.
Pancreatic ductal adenocarcinoma is the most common form of pancreatic adenocarcinoma. In the 2026 phase 1–2 daraxonrasib report, the authors note that activating RAS mutations occur in more than 90% of PDAC tumors. The later phase 3 publication likewise describes aberrant RAS-pathway activation as a key disease driver.
A pathway’s role in a cancer does not by itself determine treatment. Diagnosis, mutation testing, prior therapy, contraindications and the approved label all matter in clinical decisions.
04 · Daraxonrasib
RMC-6236 approaches the pathway through a tri-complex.
Daraxonrasib binds cyclophilin A to create a new composite surface. The resulting complex binds active RAS-GTP, forming a tri-complex that blocks RAS from engaging downstream effector proteins. This is why early literature often calls the molecule a RAS(ON) multi-selective tri-complex inhibitor.
The phase 3 RASolute 302 study compared daraxonrasib with investigator-selected chemotherapy in 500 patients with previously treated metastatic PDAC. The peer-reviewed report concluded that daraxonrasib produced significantly longer overall and progression-free survival than chemotherapy in that study population.
RASolute 302 publication at PubMed↗05 · Evidence timeline
From chemical concept to an FDA-approved ingredient.
Tri-complex chemistry
A Science paper described chemical remodeling of cyclophilin A to target active mutant KRAS.
View source ↗Translational evaluation
Cancer Discovery reported preclinical work and initial clinical translation of RMC-6236 in RAS-driven cancers.
View source ↗Advanced RAS-mutated PDAC
A phase 1–2 report in the New England Journal of Medicine evaluated daraxonrasib in previously treated disease.
View source ↗Phase 3 and FDA approval
RASolute 302 was published, followed by FDA approval of daraxonrasib as RASONQUE on 26 August.
View source ↗06 · Scope and limits
What this page is—and is not.
This page helps scientists, buyers and technical teams understand public terminology and evidence. It is not a treatment guide, a substitute for the FDA-approved label or individual medical advice.
Daraxon’s daraxonrasib material is not RASONQUE finished medicine and is restricted to qualified research, analytical or drug-registration uses.