KRASG12C IN-19 

KRASG12C IN-19 is a selective and orally active KRAS^G12C inhibitor. KRASG12C IN-19 exerts potent antiproliferative activity against the KRAS^G12C-mutant non small cell lung cancer (NSCLC) cell line H358 with an IC₅₀ of 7.6 nM, and effectively suppresses downstream ERK phosphorylation (IC₅₀ = 24.06 nM). KRASG12C IN 19 has no significant inhibitory activity against KRAS^G12V and KRAS^G12D-mutant cancer cells (PANC 1, Panc, AsPC 1, and GP2d cells) with IC₅₀ > 10,000 nM. KRASG12C IN-19 rapidly forms a covalent bond with KRAS^G12V-GDP, leading to dose-dependent inhibition of the downstream KRAS pathway. KRASG12C IN 19 can be employed for research in KRAS^G12C driven cancers, including non small cell lung cancer, pancreatic cancer, and colorectal cancer^[1].

KRASG12C IN-19 (compound 8t) has an excellent liver microsomal stability in human and mouse( T_1/2 = 188.2 and 112.3 min, C_Lint = 6.4 and 15.8 mL/min/kg)^[1].
KRASG12C IN-19 (4.88-312.5 nM, 72 h) exhibits significantly low nanomolar antiproliferative activity against H358 NSCLC cancer cells with an IC₅₀ value of 7.6 nM^[1].
KRASG12C IN-19 (4.88-312.5 nM, 72 h) not exhibits cellular potency and potency against PANC-1 (IC₅₀ > 1000 nM) (in KRASG12V cell) and Panc 03.27 (IC₅₀ > 1000 nM) (in d KRASG12D cell), and potency against AsPC-1 (IC₅₀ > 1000 nM) and GP2d (IC₅₀ > 1000 nM) cancer cells^[1].
KRASG12C IN-19 (4.88-312.5 nM, 3 h) induces dose-dependent suppression of ERK phosphorylation on H358 cells with IC₅₀ of 24.06 nM^[1].
KRASG12C IN-19 inhibits ERK phosphorylation in KRASG12C-mutant H358 cells^[1].
KRASG12C IN-19 (4.88-312.5 nM) has low toxicity potential toward hERG with IC₅₀ > 30 μM in CHO cell line^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

KRASG12C IN-19 (30 mg/kg, p.o., once daily for 29 days) suppresses the growth of human H358 NSCLC cell-derived xenograft tumors bearing the KRAS^G12C mutation in female BALB/c mice without inducing observable toxic side effects^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

590.65

C₃₃H₃₁FN₈O₂

2915282-32-3

C=CC(N1C[C@@H](N(C[C@H]1C)C2=NC(N(C3=C2C=C(C(C4=CC=CC=C4F)=N3)C#N)C5=C(N=CN=C5C6CC6)C7CC7)=O)C)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Fang Yang, et al.Design, synthesis and evaluation of 1,2-dihydropyrido[2,3-d]pyrimidine-6‑carbonitrile derivatives as novel covalent inhibitors for the treatment of KRASG12C-mutant NSCLC,Bioorganic Chemistry,