RMC-4998

SKU: orb2277607

Description

RMC-4998 is an orally bioavailable inhibitor that selectively targets the active, GTP-bound state of the KRASG12C mutant. By forming a ternary complex with intracellular cyclophilin A (CYPA), it disrupts the ERK signaling pathway to induce apoptosis, making it a valuable tool for investigating KRAS-driven cancers in both in vitro and in vivo research models.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2642037-07-6
• MW: 983.25
• Purity: 99.11% (May vary between batches)
• Formula: C₅₇H₇₄N₈O₇
• SMILES: O=C(N1CC[C@@]2(C1)C(N(C(C(C)C)C(NC3C(N4N[C@@H](CCC4)C(OCC(C)(CC5=C(C6=C([C@@H](C)OC)N=CC=C6)N(CC)C7=CC=C(C8=CC(C3)=CC=C8)C=C57)C)=O)=O)=O)CC2)=O)C#CC(C)(C)N(C)C
• Target: Apoptosis,Ras,mTOR,Kras,PI3K,ERK
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:3.3 mg/mL (3.36 mM);DMSO:80 mg/mL (81.36 mM)

Bioactivity

• Target IC50:
  KRASG12C-GTP:1–10 nM
• In Vivo:
  In H358 xenograft mouse models, oral administration of RMC-4998 significantly inhibited tumor growth or induced regression, accompanied by ERK pathway suppression and apoptosis induction. In KRASG12C-mutant NSCLC xenograft models (such as H2122, H2030, and multiple PDX models), oral administration of RMC-4998 (80 mg/kg, once daily) delayed tumor growth, while combination with the mTORC1 inhibitor RMC-6272 (6 mg/kg, intraperitoneally, once weekly) induced deep and durable complete tumor regressions without notable weight loss or hyperglycemia-related toxicity.
• In Vitro:
  RMC-4998 is a selective KRASG12C inhibitor that forms a ternary complex with cyclophilin A and KRASG12C-GTP, enabling rapid covalent modification and inhibition of KRASG12C (IC₅₀ = 1–10 nM). RMC-4998 disrupts KRAS interactions with downstream effectors such as CRAF and SOS, effectively suppressing ERK signaling. RMC-4998 remains active even under RTK stimulation (e.g., EGF or HGF) and shows no activity against wild-type KRAS, NRAS, or HRAS.

Storage & Handling

• Storage: 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

RMC4998

Compound Identifiers

PubChem CID

176455331