RMC-7977

SKU: orb1943501

Description

RMC-7977 is a potent and selective inhibitor targeting the active GTP-bound state of KRAS, HRAS, and NRAS. It is a research tool for investigating KRAS G12C-mutant solid tumors, with demonstrated utility in both in vitro cellular assays and in vivo xenograft models to study oncogenic RAS signaling and therapeutic potential.

Research Area

Cell Biology, Epigenetics & Chromatin, Molecular Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2765082-12-8
• MW: 865.09
• Purity: 98.20% (May vary between batches)
• Formula: C₄₇H₆₀N₈O₆S
• SMILES: O=C1OCC(C)(C)CC=2C3=CC(=CC=C3N(C2C=4C=C(C=NC4C(OC)C)N5CCN(CC5)C6CC6)CC)C=7N=C(SC7)CC(NC(=O)C8C9COCC89)C(=O)N%10NC1CCC%10
• Target: Kras
• Solubility: DMSO:120 mg/mL (138.71 mM)

Bioactivity

• In Vivo:
  METHODS: U2OS cells were treated with 50 nM RMC-7977 to observe the formation of KRAS-CYPA complexes and disruption of KRAS(G12V)-CRAF interactions using a live-cell nano-bioluminescence resonance energy transfer (BRET) kinetic assay. RESULTS: RMC-7977 induced KRAS and CYPA binding and dissociated the CRAF RBD from KRAS at the same fast rate (signaling half-life (t1/2) < 5 min). METHODS: RAS-dependent (KRAS, NRAS, or EGFR mutated) cancer cells treated with RMC-7977 (0.1,1,10,100,100 nM) were compared for activity of RMC-7977 in cancer cells harboring various activating mutations in the RAS pathway, specifically oncogenic variants of KRAS, NRAS, EGFR, or BRAF. RESULTS: Exhibited concentration-dependent inhibition of downstream signaling and proliferation in the low nanomolar range.
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• In Vitro:
  METHODS: U2OS cells were treated with 50 nM RMC-7977 to observe the formation of KRAS-CYPA complexes and disruption of KRAS(G12V)-CRAF interactions using a live-cell nano-bioluminescence resonance energy transfer (BRET) kinetic assay. RESULTS: RMC-7977 induced KRAS and CYPA binding and dissociated the CRAF RBD from KRAS at the same fast rate (signaling half-life (t1/2) < 5 min). METHODS: RAS-dependent (KRAS, NRAS, or EGFR mutated) cancer cells treated with RMC-7977 (0.1,1,10,100,100 nM) were compared for activity of RMC-7977 in cancer cells harboring various activating mutations in the RAS pathway, specifically oncogenic variants of KRAS, NRAS, EGFR, or BRAF. RESULTS: Exhibited concentration-dependent inhibition of downstream signaling and proliferation in the low nanomolar range.
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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

Compound Identifiers

PubChem CID

171361118