MK-8033

MK-8033 is an orally active ATP competitive c-Met/Ron dual inhibitor (IC₅₀s: 1 nM (c-Met),7 nM (Ron)), with preferential binding to the activated kinase conformation. MK-8033 can be used in the research of cancers, such as breast and bladder cancers, non-small cell lung cancers (NSCLCs)^[1][2]. IC50 & Target: IC50: 7 nM (Ron)^[1] In Vitro: MK-8033 (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4)^[1].
MK-8033 (1 μM, 2 h) inhibits phosphorylation of Y1349 of c-Met (IC₅₀: 0.03 μM) in the c-Met dependent gastric cancer cell line GTL-16^[1].
MK-8033 (1-10 μM, 72 h) inhibits GTL-16 cell proliferation (IC₅₀: 0.58 μM)^[1].
MK-8033 binds more tightly to phosphorylated c-Met (K_d: 3.2 nM) than to its unphosphorylated counterpart (K_d: 10.4 nM), and inhibits oncogenic c-Met activation loop mutants with IC₅₀s ranging from 0.6 to 1 nM^[1].
MK-8033 (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells^[2].
MK-8033 (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation^[2].
MK-8033 (10 μM, 6 h) enhances γ-H2Ax levels in A549 cells compared to double irradiation and decreases in DNA repair^[2].
MK-8033 (2 μM, 72 h) results in reduced cell proliferation, but modest induction of apoptosis in G-alpha protein mutant UM (uveal melanoma) cells^[3].
In Vivo: MK-8033 (Compound 11r, oral administration, 3-100 mg/kg, twice daily for 21 days) inhibits tumor growth in GTL-16 c-Met amplified gastric tumor xenografts^[1].
MK-8033 exhibits moderate clearance (t_1/2: 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% for rats, 33% for dog)^[1].