Sotorasib

SKU: orb1298716

Description

Sotorasib

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2296729-00-3
• MW: 560.594
• Purity: 99.36%
• 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: Kras,Ras
• 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 bearin the human pancreatic cancer tumor MIA PaCa-2 T2 o the human lung cancer tumor NCI-H358. Results: Sotorasib significantly inhibite 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 o 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 usin the CellTiter-Glo Luminescent Cell Viability Assay kit. Results: Sotorasib impaire 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, an 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% o 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.
• 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