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MedChemExpress - Model MK-8033 - 1001917-37-8

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].

MK-8033

MCE China：MK-8033

Brand：MedChemExpress (MCE)

Cat. No.HY-13299

CAS：1001917-37-8

Purity：98.34%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month

Shipping：Room temperature in continental US; may vary elsewhere.

Description：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).

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 (Kd: 3.2 nM) than to its unphosphorylated counterpart (Kd: 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 (t1/2: 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% for rats, 33% for dog)[1].

IC50 & Target：Ron 7 nM (IC50)

References：

[1]. Northrup AB, et al, Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): A Specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated [Content Brief]

[2]. Bhardwaj V, et al. C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression. J Thorac Oncol. 2012 Aug;7(8):1211-7. [Content Brief]

[3]. Chandrani Chattopadhyay, et al. Simultaneous inhibition of the HGF/MET and Erk1/2 pathways affect uveal melanoma cell growth and migration. PLoS One. 2014 Feb 13;9(2):e83957. [Content Brief]

Brand introduction:
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