For research use only. Not for therapeutic Use.
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 (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].
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].
| Catalog Number | I000076 |
| CAS Number | 1001917-37-8 |
| Synonyms | 1-[5-(1-methylpyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-14-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide |
| Molecular Formula | C25H21N5O3S |
| Purity | ≥95% |
| InChI | InChI=1S/C25H21N5O3S/c1-30-15-20(13-28-30)19-11-23-24(27-12-19)8-7-18-6-5-17(10-22(18)25(23)31)16-34(32,33)29-14-21-4-2-3-9-26-21/h2-13,15,29H,14,16H2,1H3 |
| InChIKey | VMJFTOSOFDEKTM-UHFFFAOYSA-N |
| SMILES | CN1C=C(C=N1)C2=CC3=C(C=CC4=C(C3=O)C=C(C=C4)CS(=O)(=O)NCC5=CC=CC=N5)N=C2 |
| Reference | [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 [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. [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. |
