Adagrasib (MRTX849) is an orally active and selective covalent inhibitor of KRAS G12C. Adagrasib binds to the GDP state of the inactive conformation of KRAS G12C and inhibits KRAS and its downstream signaling. Adagrasib exhibits inhibitory activity against KRAS G12C mutant tumors.

Apixaban (human liver microsomes):117.40 μM, Apixaban (rat liver microsomes):7.99 μM

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. [1]
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. [2]

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. [1]
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. [3]

DMSO: 242 mg/mL (400.58 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 10 mg/mL (16.55 mM), Suspension.