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].
MK-8033 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H460 cells
0.1-10 μM
2 hours
MK-8033 did not affect the phosphorylation of c-Met, ERK, and Akt
J Thorac Oncol. 2012 Aug;7(8):1211-7
A549 cells
0.1-10 μM
2 hours
MK-8033 did not affect the phosphorylation of c-Met, ERK, and Akt
J Thorac Oncol. 2012 Aug;7(8):1211-7
H1993 cells
0.1-10 μM
2 hours
MK-8033 downregulated the phosphorylation of c-Met, ERK, and Akt
J Thorac Oncol. 2012 Aug;7(8):1211-7
EBC-1 cells
0.1-10 μM
2 hours
MK-8033 downregulated the phosphorylation of c-Met, ERK, and Akt
J Thorac Oncol. 2012 Aug;7(8):1211-7
wild-type uveal melanoma cells
2.5 μM
72 hours
To evaluate the effect of METi on cell migration, results showed that METi significantly inhibited migration in wild-type cells.
PLoS One. 2014 Feb 13;9(2):e83957
GNAQ mutant uveal melanoma cells
2.5 μM
72 hours
To evaluate the effect of METi on cell migration, results showed that METi significantly inhibited migration in GNAQ mutant cells.
PLoS One. 2014 Feb 13;9(2):e83957
wild-type uveal melanoma cells
2.5 μM
72 hours
To evaluate the effect of METi on cell proliferation, results showed no significant effect of METi alone on wild-type cells.
PLoS One. 2014 Feb 13;9(2):e83957
GNAQ mutant uveal melanoma cells
2.5 μM
72 hours
To evaluate the effect of METi on cell proliferation, results showed that METi alone reduced proliferation in GNAQ mutant cells.
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