Adagrasib

SKU: orb1298993

Description

Adagrasib

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2326521-71-3
• MW: 604.12
• Purity: 99.90%
• Formula: C₃₂H₃₅ClFN₇O₂
• SMILES: CN1CCC[C@H]1COc1nc2CN(CCc2c(n1)N1CCN([C@@H](CC#N)C1)C(=O)C(F)=C)c1cccc2cccc(Cl)c12
• Target: Ras,Kras
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:10 mg/mL (16.55 mM);DMSO:242 mg/mL (400.58 mM)

Bioactivity

• Target IC50:
  Apixaban (rat liver microsomes):7.99 μM|Apixaban (human liver microsomes):117.40 μM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Adagrasib (1-100 mg/kg, 10% Captisol in 10 mM citrate buffer pH 5.0) was administered by gavage to athymic nude mice harboring human pancreatic adenocarcinoma tumor MIA PaCa-2 or human lung adenocarcinoma tumor H358 once daily for 16-22 days. RESULTS: MRTX849 showed dose-dependent antitumor efficacy in a well-tolerated dose range. METHODS: To assay in vivo antitumor activity, Adagrasib (30 mg/kg orally) and paclitaxel (18 mg/kg intraperitoneally) were administered every three days for four weeks to athymic nude mice harboring tumors of ABCB1-mediated MDR xenografts. RESULTS: Tumors were resistant to Adagrasib and paclitaxel alone and did not show significant antitumor effects.Combined treatment with Adagrasib and paclitaxel showed stronger inhibition of tumor growth.
• In Vitro:
  METHODS: Seventeen KRAS G12C mutant and three non-KRAS G12C mutant tumor cells were treated with Adagrasib (0-10 μM) for 3 days, and cell viability was measured in 2D culture using CellTiter-Glo assay. RESULTS: MRTX849 effectively inhibited cell growth in the majority of KRAS G12C mutant cell lines, with IC50 values ranging from 10-973 nM. three non-KRAS G12C mutant cells had IC50 values greater than 1 μM. METHODS: Human lung cells NCI-H358 were treated with Adagrasib for 3 h, and the target inhibitory activity was detected by Cell-Based Phospho-ERK Assay. RESULTS: Adagrasib inhibited the p-ERK level of NCI-H358, and the IC50 was 14 nM.

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

state, selective, Ras, covalent, cells, Adagrasib, anti-tumor, H1373, G12C, Inhibitor, GDP-bound, inhibit, mutant, MRTX 849, inactive, MRTX849, MRTX-849, KRAS G12C, KRAS, MIA PaCa-2

Compound Identifiers

PubChem CID

138611145