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• 產品描述： 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)

• 靶點： Ron:7 nM (IC50);c-Met/HGFR

• 體外研究：
  MK-8033 (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4). 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). 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. MK-8033 (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells. MK-8033 (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation. MK-8033 (10 μM, 6 h) enhances γ-H2Ax levels in A549 cells compared to double irradiation and decreases in DNA repair. 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. Western Blot Analysis Cell Line: EBC-1, H1993 cells, A549 and H460 cells Concentration: 0.1, 1, 10 μM Incubation Time: 2 h Result: Reduced the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells in a dose-dependent manner.

• 體內研究：
  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. 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). Animal Model: Human GTL-16 c-Met amplified gastric tumor xenografts Dosage: 3, 10, 30, and 100 mg/kg Administration: Oral administration, twice daily for 21 days Result: Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively.Inhibited c-Met (Y1349) phosphorylation.

• 參考文獻：
  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 state of c-Met. J Med Chem. 2013 Mar 28;56(6):2294-310. 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.

• 溶解性： soluble  in  DMSO

• 保存條件： -20℃

• 配置溶液濃度參考：
  

  	1mg	5mg	10mg
  1 mM	2.121 ml	10.604 ml	21.208 ml
  5 mM	0.424 ml	2.121 ml	4.242 ml
  10 mM	0.212 ml	1.06 ml	2.121 ml
  50 mM	0.042 ml	0.212 ml	0.424 ml

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本計算器可幫助您計算出特定溶液中溶質的質量、溶液濃度和體積之間的關系，公式為：

質量 (mg) = 濃度 (mM) x 體積 (mL) x 分子摩爾量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *