Daraxonrasib/RMC-6236/CAS 2765081-21-6/API
Daraxonrasib (RMC-6236)
First-in-Class Oral RAS(ON) Multi-Selective Inhibitor · A New Breakthrough in Pancreatic Cancer
1. Product Overview
Item | Details |
Product Name | 达拉索拉西布/Daraxonrasib |
International Nonproprietary Name | Daraxonrasib |
Research Code | RMC-6236 |
Brand Name | RASONQUE |
CAS Number | 2765081-21-6 |
Molecular Formula | C44H58N8O5S |
Molecular Weight | 811.06 g/mol |
SMILES | CCN1C2=C3C=C(C=C2)C4=CSC(=N4)C[C@@H](C(=O)N5CCC[C@H](N5)C(=O)OCC(CC3=C1C6=C(N=CC(=C6)N7CCN(CC7)C)[C@H](C)OC)(C)C)NC(=O)[C@H]8C[C@@H]8C |
Patent / Developing Company | Revolution Medicines, Inc. (USA) |
Drug Class | Oral small-molecule RAS(ON) multi-selective inhibitor ("molecular glue" tri-complex inhibitor) |
Indications / Use | Advanced solid tumors harboring RAS mutations (G12X, G13X, Q61X), with a primary focus on pancreatic ductal adenocarcinoma (PDAC); also under investigation in RAS-driven NSCLC and colorectal cancer |
Packaging & Storage | Oral tablets (300 mg), once daily; store at 20–25 °C (excursions permitted 15–30 °C); 24-month shelf life |
Regulatory Status | US FDA: approved 26 Aug 2026 (2L metastatic pancreatic adenocarcinoma); EMA: positive CHMP opinion 15 Oct 2026, awaiting EC approval; 1L, adjuvant and other RAS-mutant settings in global Phase III |
Chemical Structure
2. Pancreatic Cancer Treatment: Mechanism of Action & Efficacy
2.1 Mechanism of Action
RMC-6236 inhibits RAS signaling through a unique "molecular glue" mechanism: the drug first binds cyclophilin A (CypA), an intracellular chaperone protein, to form a binary complex; this complex then engages the active, GTP-bound state of RAS (RAS(ON)), creating a stable non-covalent tri-complex.
Formation of the tri-complex prevents RAS(ON) from engaging downstream effectors such as RAF and PI3K, thereby blocking RAS→RAF/MEK/ERK and PI3K/AKT/mTOR signaling and suppressing tumor cell proliferation and survival.
Unlike KRAS G12C-selective inhibitors (e.g., sotorasib), daraxonrasib targets the RAS(ON) state without depending on a specific mutation, simultaneously inhibiting G12D, G12V, G12R, G13X, Q61X and other variants and overcoming resistance driven by secondary mutations. Over 90% of pancreatic cancers are RAS-mutated, giving the drug broad coverage potential.
Mechanism: Daraxonrasib–CypA–RAS(ON) tri-complex blocks RAF binding
2.2 Efficacy Analysis (Phase 3 RASolute 302, NCT06625320)
RASolute 302 was a global, randomized, controlled Phase 3 registrational trial enrolling 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC), comparing oral daraxonrasib (300 mg once daily) with investigator's choice of standard chemotherapy. The trial met all primary endpoints (OS and PFS) at the first interim analysis and was stopped early; full results were presented orally at the ASCO 2026 Annual Meeting (May 31, 2026) and simultaneously published in the New England Journal of Medicine.
Key conclusion: daraxonrasib raised median overall survival in 2L metastatic pancreatic cancer above one year for the first time, reducing the risk of death by approximately 60% — the most important treatment advance in this disease in over a decade and a potential new standard of care.
Endpoint | Daraxonrasib Arm | Chemotherapy Control |
Median Overall Survival (mOS) | 13.2 months | 6.7 months |
Median Progression-Free Survival (mPFS) | 7.2 months | 3.6 months |
Objective Response Rate (ORR) | ~30–33% | ~11% |
Hazard Ratio (HR) | OS 0.40 (p<0.0001) | 60% reduction in risk of death |
Discontinuation due to AEs | 1.2% | 11.2% |
3. US Product Information
Item | Details |
Brand Name | RASONQUE (daraxonrasib) tablets |
Agency / Approval Date | US FDA, August 26, 2026 |
NDA Number | 220910 |
License Holder | Revolution Medicines, Inc. (Redwood City, CA) |
Indication | Adults with metastatic pancreatic adenocarcinoma after ≥1 prior systemic therapy, or not candidates for multiagent systemic therapy |
Dosage & Administration | Oral, 300 mg once daily (per Prescribing Information) |
Storage | 20–25 °C; excursions permitted to 15–30 °C |
Shelf Life | 24 months from date of manufacture |
Regulatory Designations | Breakthrough Therapy, Orphan Drug, National Priority Voucher |
On August 26, 2026, the US FDA approved daraxonrasib (brand name: RASONQUE, NDA 220910) for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy — the first approved RAS-targeted therapy in this setting.
Previously, the drug received FDA Breakthrough Therapy designation (June 2025), Orphan Drug designation and a National Priority Voucher, which accelerated its review.
The most common adverse reaction is rash (incidence ~85.5%; Grade ≥3 ~13.7%); overall safety and tolerability were favorable, with a substantially lower discontinuation rate than chemotherapy.
Please refer to the current FDA Prescribing Information for dosing details.
Note:
Qingdao Qingmei Biotech Co., Ltd. supplies Daraxonrasib (RMC-6236) exclusively for research and educational purposes, and solely for markets outside of China.
In accordance with patent laws and pharmaceutical regulations, Daraxonrasib (RMC-6236) is not permitted for use on individuals or in human clinical research at this time.