Sotorasib

SKU: orb1298716

Description

Sotorasib (AMG-510) is a selective, covalent inhibitor that targets the inactive, GDP-bound form of the KRAS G12C mutant. It potently suppresses oncogenic KRAS signaling and has demonstrated antitumor efficacy in both cellular assays and in vivo models, supporting its use in cancer research.

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2296729-00-3
• MW: 560.594
• Purity: 99.95% (May vary between batches)
• Formula: C₃₀H₃₀F₂N₆O₃
• SMILES: O=C1N=C(C=2C=C(F)C(=NC2N1C=3C(=NC=CC3C)C(C)C)C=4C(F)=CC=CC4O)N5CCN(C(=O)C=C)CC5C
• Target: Ras,Kras
• Solubility: H2O:33.33 mg/mL (59.45 mM);DMSO:247.5 mg/mL (441.5 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (8.92 mM)

Bioactivity

• Target IC50:
  KRas (G12C) (CLM22 organoids):10.95 μM|KRas (G12C) (CWH22 organoids):12.07 μM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Sotorasib (3-100 mg/kg) was orally administered once daily for four weeks to athymic nude mice bearing the human pancreatic cancer tumor MIA PaCa-2 T2 or the human lung cancer tumor NCI-H358. RESULTS: Sotorasib significantly inhibited the growth of MIA PaCa-2 T2 and NCI-H358 tumors at all doses, and tumor regression was observed at higher doses. METHODS: To assay antitumor activity in vivo, Sotorasib (30 mg/kg in 0.5% sodium carboxymethylcellulose, administered by gavage once daily) and Cisplatin (4 mg/kg in 0.9% saline, intraperitoneally every two days) were administered to Balb/C nude mice harboring human lung cancer tumors. RESULTS: Tumor shrinkage in the combination group was more than twice that of the single-administration group.
• In Vitro:
  METHODS: Twenty-two tumor cells were treated with Sotorasib (0-10 μM) for 72 h. Cell viability was measured using the CellTiter-Glo Luminescent Cell Viability Assay kit. RESULTS: Sotorasib impaired the growth of all KRAS G12C cell lines except SW1573, with IC50 values ranging from 0.004-0.032 μM. non-KRAS G12C cell lines were sensitive to Sotorasib, with an IC50 >7.5 μM. METHODS: KRAS G12C mutant tumor cells were treated with Sotorasib (100 nM) for 4-72 h, and the expression levels of target proteins were detected using Western Blot method. RESULTS: Sotorasib rapidly inhibited KRAS downstream signaling, but p-ERK levels returned to 75% of the baseline level at 72 h. Sotorasib was also shown to rapidly inhibit KRAS downstream signaling.

Storage & Handling

• Storage: 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

Sotorasib, phosphorylation, regression, Ras, anti-tumour, AMG510, AMG-510, AMG 510, covalent, NSCLC, KRAS, KRAS G12C, inhibit, mutation, G12C, GDP-bound, Inhibitor

Compound Identifiers

PubChem CID

138461166