Zoldonrasib

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: O=C1OCC(C)(C)CC=2C3=CC(=CC=C3N(C2C4=CC(=CN=C4C(OC)C)N5CCN(CC5)C6CC6)CC(F)(F)F)N7CCOC(C7)CC(NC(=O)C(N8CCC9(CN(C(=O)C%10N(C)C%10C%11CC%11)CC9)C8)C%12CCCC%12)C(=O)N%13NC1CCC%13
• Target: Apoptosis,Kras,Ras
• 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.
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• 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.
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Storage & Handling

• Storage: -20°C
• 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