Daraxonrasib

SKU: orb1982704

Description

Daraxonrasib (RMC-6236) is a novel, orally bioavailable inhibitor that targets multiple RAS variants in their active GTP-bound state. This investigational compound demonstrates anti-tumor activity in preclinical models, supporting its use in research on RAS-driven cancers, including in vitro cellular assays and in vivo xenograft studies.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2765081-21-6
• MW: 811.05
• Purity: 99.96%
• Formula: C₄₄H₅₈N₈O₅S
• 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
• Target: PERK,Ras
• Solubility: DMSO:200 mg/mL (246.59 mM);10% DMSO+40% PEG300+5% Tween-80+45% Saline:5 mg/mL (6.16 mM)

Bioactivity

• Target IC50:
  KRAS (WT):154 nM (KD2)|CYPA:55.3 nM (KD1)|KRas (G12D):364 nM (KD2)|KRAS (G12V):131 nM (KD2)
• In Vivo:
  METHODS: Daraxonrasib (RMC-6236) (3, 10, 25 mg/kg, oral) was administered to mice bearing Capan-2 xenograft tumors. The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of RMC-6236 as well as its antitumor activity in vivo in a range of mutant RAS-driven human tumor xenograft models were evaluated. RESULTSDaraxonrasib (RMC-6236) exhibited similar PK profiles in multiple xenograft models and did not accumulate in the blood and tumors after repeated dosing; RMC-6236 exposure in various xenograft tumors was approximately 3 to 7 times higher than that in the blood and was cleared relatively slowly from the tumors; consistent with the dose-dependent and prolonged exposure in xenograft tumors, oral administration of RMC-6236 resulted in dose-dependent and persistent inhibition of RAS pathway signaling.
• In Vitro:
  METHODS: HPAC and Capan-2 cell lines were treated with Daraxonrasib (RMC-6236) (1, 3, 10, 30 nM, 4 hours) and Western Blot analysis was performed. RESULTS Time- and concentration-dependent inhibition of RAS pathway signaling markers pERK, pAKT, and pS6 were observed in HPAC and Capan-2 cell lines treated with Daraxonrasib (RMC-6236). The inhibition of pERK and pS6 in Capan-2 cells lasted for at least 48 hours. HPAC cells also showed sustained pERK inhibition and time-dependent induction of apoptosis.

Storage & Handling

• Storage: keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RAS-IN-2, Ras, RMC6236, RMC-6236, RMC-6236

Compound Identifiers

PubChem CID

164885345