MK-8033 hydrochloride is an orally active dual inhibitor targeting c-Met and Ron kinases competitively with ATP (IC50s: 1 nM (c-Met),7 nM (Ron)), showing a preference for the activated kinase conformation. MK-8033 hydrochloride is applicable in cancer research, including breast and bladder cancers, as well as non-small cell lung cancers (NSCLCs)[1][2].
体内研究
MK-8033 hydrochloride (oral administration, 3-100 mg/kg, twice daily for 21 days) suppresses tumor growth in GTL-16 gastric tumor xenografts with c-Met amplification[1].
MK-8033 hydrochloride demonstrates moderate clearance (t1/2: 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% in rats, 33% in dogs)[1].
体外研究
MK-8033 hydrochloride at a concentration of 10 μM, exhibited 31% inhibition of CYP3A4 (cytochrome P450 3A4)[1].
MK-8033 hydrochloride (1 μM, 2 h) suppresses the phosphorylation of Y1349 of c-Met (IC50: 0.03 μM) in the c-Met dependent gastric cancer cell line GTL-16[1].
MK-8033 hydrochloride (1-10 μM, 72 h) suppresses the proliferation of GTL-16 cells (IC50: 0.58 μM)[1].
MK-8033 hydrochloride exhibits higher binding affinity to phosphorylated c-Met (Kd: 3.2 nM) compared to its unphosphorylated form (Kd: 10.4 nM). Additionally, it inhibits oncogenic c-Met activation loop mutants with IC50 values ranging from 0.6 to 1 nM[1].
MK-8033 hydrochloride (0.1-10 μM, 2 h) decreases the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells[2].
MK-8033 hydrochloride (1 μM, 1 h) enhances the sensitivity of EBC-1 and H1993 cells (high c-Met-expressing) to radiation[2].
MK-8033 hydrochloride (10 μM, 6 h) increases γ-H2Ax levels in A549 cells compared to double irradiation and attenuates DNA repair[2].
MK-8033 hydrochloride (2 μM, 72 h) leads to decreased cell proliferation, with modest induction of apoptosis in G-alpha protein mutant UM (uveal melanoma) cells[3].
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