(S)-AMG-510

SKU: orb1306045

Description

(S)-AMG-510 is the stereoisomer of the clinical drug Sotorasib, functioning as a selective, covalent inhibitor of the KRAS G12C oncoprotein. It is a valuable research tool for investigating KRAS-driven tumor biology in both cellular and animal models, supporting translational oncology studies.

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2252403-56-6
• MW: 560.594
• Purity: 99.76% (May vary between batches)
• Formula: C₃₀H₃₀F₂N₆O₃
• SMILES: O=C1N(C=2C(C(=N1)N3[C@@H](C)CN(C(C=C)=O)CC3)=CC(F)=C(N2)C4=C(F)C=CC=C4O)C5=C(C(C)C)N=CC=C5C
• Target: Kras,p38 MAPK,Ras
• Solubility: DMSO:5.61 mg/mL (10.01 mM)

Bioactivity

• In Vivo:
  METHODS: (S)-AMG-510 (10 mg/kg, oral) or sotorasib (10 mg/kg) + encorafenib (20 mg/kg) were used to treat NOD/SCID mice bearing tumor xenografts. The body weight and tumor size of the mice were monitored every 2 days. RESULTS (S)-AMG-510 withdrawal and the combination of BRAF inhibitors induced tumor regression in vivo.
• In Vitro:
  METHODS: KRAS G12 mutant NSCLC cell lines (NCI-H358 [G12C], NCI-H23 [G12C], NCI-H2122 [G12C], A549 [G12S], NCI-H2009 [G12A], NCI-H441 [G12V], and SK-LU1 [G12D]) were treated with (S)-AMG-510 (0.001-100000nM, 72 hours), and cell viability was detected by CCk8. RESULTS All non-G12C cell lines were as expected. Among KRAS G12 C cells, H358 and H2122 were sensitive, but H23 cells were resistant to (S)-AMG-510. METHODS: Engineered Ba/F3 cells carrying KRAS G12C were treated with (S)-AMG-510 (0.001-100000nM, 72 hours), and cell viability was determined by CCK8. RESULTS Ba/F3 cells expressing KRAS G12C were sensitive to sotorasib with an IC50 value of 12.4nM. METHODS: Ba/F3 cells expressing KRAS G12C or G12D were treated with (S)-AMG-510 (10-100nM, 6 hours) or adagrasib and immunoblotted. RESULTS (S)-AMG-510 inhibited pERK and pS6 levels in Ba/F3 cells expressing KRAS G12C; it had no effect on KRAS G12D.

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

Inhibitor, inhibit, KRAS G12C, AMG-510, AMG-510 racemate, AMG510, AMG 510, (S)-Sotorasib, Ras, Sotorasib, Sotorasib racemate

Compound Identifiers

PubChem CID

137278711