MK-8033 hydrochloride 是一种具有口服活性的 ATP 竞争性 c-Met/Ron 双重抑制剂 (IC₅₀s: 1 nM (c-Met)，7 nM (Ron))，优先结合活化的激酶构象 (activated kinase conformation)。MK-8033 hydrochloride 可用于癌症的研究，例如乳腺癌，膀胱癌、非小细胞肺癌 (NSCLC)。

MK-8033 hydrochloride is an orally active ATP competitive c-Met/Ron dual inhibitor (IC 50 s: 1 nM (c-Met),7 nM (Ron)), with preferential binding to the activated kinase conformation. MK-8033 hydrochloride can be used in the research of cancers, such as breast and bladder cancers, non-small cell lung cancers (NSCLCs).

Solid

IC50: 7 nM (Ron)

MK-8033 hydrochloride (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4).
MK-8033 hydrochloride (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.
MK-8033 hydrochloride (1-10 μM, 72 h) inhibits GTL-16 cell proliferation (IC50: 0.58 μM).
MK-8033 hydrochloride 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.
MK-8033 hydrochloride (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells.
MK-8033 hydrochloride (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation.
MK-8033 hydrochloride

MK-8033 hydrochloride (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.
MK-8033 hydrochloride 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). has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[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.

In Vitro: H₂O : 7.14 mg/mL (14.06 mM; Need ultrasonic)DMSO : 5.88 mg/mL (11.58 mM; Need ultrasonic)配制储备液