RMC-9805

SKU: orb1944618

Description

RMC-9805 is a covalent, oral, and mutant-selective inhibitor targeting the active state of KRASG12D. It functions by forming a stable, high-affinity complex with KRASG12D and cyclophilin A, blocking downstream signaling. This mechanism has demonstrated induction of apoptosis and tumor regression in preclinical in vivo and in vitro models of KRASG12D-driven cancers.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2922732-54-3
• MW: 1168.44
• Purity: 99.99% (May vary between batches)
• Formula: C₆₃H₈₈F₃N₁₁O₇
• SMILES: C(C(F)(F)F)N1C(=C2C=3C1=CC=C(C3)N4C[C@](C[C@H](NC([C@@H](N5C[C@@]6(CC5)CN(C(=O)[C@H]7[C@H](N7C)[C@@H]8CC8)CC6)[C@H]9CCCC9)=O)C(=O)N%10N[C@](C(=O)OCC(C)(C)C2)(CCC%10)[H])(OCC4)[H])C%11=C([C@@H](OC)C)N=CC(=C%11)N%12CCN(CC%12)C%13CC%13
• Target: Apoptosis,Ras,Kras
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (4.28 mM);DMSO:252.5 mg/mL (216.1 mM)

Bioactivity

• Target IC50:
  pERK (HPAC cells):7 nM|pERK (HPAC cells):7 nM (EC50)|pERK (AsPC-1 cells):23 nM (EC50)
• In Vivo:
  METHODS: To detect in vivo anti-tumor activity, RMC-9805 (100 mg/kg) was orally administered to eCT26 (KRASG12D/G12D) xenograft tumor mice once a day for 4-8 days. RESULTS: RMC-9805 exhibits anti-tumor activity in the KRAS G12D xenograft model.
• In Vitro:
  METHODS: eCT26 (KRASG12D/G12D) and KPCY 6499c4 (KRASG12D/+) cells were treated with RMC-9805 (100 nM) for 48 hours, and cytokine levels were measured using a cytokine array. Cell surface expression was detected by flow cytometry. RESULTS: CXCL1 and GM-CSF were reduced in eCT26 (KRASG12D/G12D) and KPCY 6499c4 (KRASG12D/+) cells, while PD-L1 and PVR were reduced; CXCL10 and CCL17 increased, while MHC-I and MHC-II increased.

Storage & Handling

• Storage: keep away from moisture,store at low temperature,keep away from direct sunlight | 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

KRAS G12D, KRAS G12D IN 18, KRAS G12D inhibitor 18, Zoldonrasib

Compound Identifiers

PubChem CID

168201327