MK-8033 hydrochlorideC-Met/Ron inhibitor CAS# 1283000-43-0 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1283000-43-0 | SDF | Download SDF |
| PubChem ID | 51030992 | Appearance | Powder |
| Formula | C25H22ClN5O3S | M.Wt | 507.99 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : < 1 mg/mL (insoluble or slightly soluble) | ||
| Chemical Name | 1-[2-(1-methylpyrazol-4-yl)-11-oxobenzo[1,2]cyclohepta[2,4-b]pyridin-9-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide;hydrochloride | ||
| SMILES | CN1C=C(C=N1)C2=CN=C3C=CC4=C(C=C(C=C4)CS(=O)(=O)NCC5=CC=CC=N5)C(=O)C3=C2.Cl | ||
| Standard InChIKey | BKIQDRGTLKPYCL-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C25H21N5O3S.ClH/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;1H | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | MK8033 Hcl is a novel and specific dual ATP competitive c-Met/Ron inhibitor (IC50=1 nM Wt c-Met) under investigation as a treatment for cancer.
IC50 Value: 1 nM (Wt c-Met); 2.0 nM (c-Met N1100Y) [1]
Target: c-Met
in vitro: MK-8033 binds 3-fold more tightly to phosphorylated c-Met kinase domain (Kd= 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). Signigicantly, MK-8033 potently inhibits kinase activity of three oncogenic c-Met activation loop mutants, Y1230C, Y1230H, and Y1235D (IC50s ranging from 0.6 to 1 nM at 50 uM ATP) in addition to other c-Met activating mutants N1100Y and M1250T. MK-8033 potently inhibited GTL-16 proliferation with an IC50 of 582 ± 30 nM. By contrast the HCT116 cell line, which does not harbor basal c-Met activation, was not inhibited by MK-8033 (IC50 > 10000 nM) [1]. MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells [2].
in vivo: MK-8033 was orally dosed in GTL-16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p-Met (Y1349) in tumors and MK-8033 concentrations in plasma. At 100 mg/kg,essentially complete inhibition of p-Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK-8033 level and Met pY1349. Treatment with escalating dosed of MK-8033 for 21 days lead to antitumor efficacies in a dose-dependent manner. Dosing at 3, 10, 30, and 100 mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to tumor from vehicle-treated mice. References: | |||||
MK-8033 hydrochloride Dilution Calculator
MK-8033 hydrochloride Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9685 mL | 9.8427 mL | 19.6854 mL | 39.3709 mL | 49.2136 mL |
| 5 mM | 0.3937 mL | 1.9685 mL | 3.9371 mL | 7.8742 mL | 9.8427 mL |
| 10 mM | 0.1969 mL | 0.9843 mL | 1.9685 mL | 3.9371 mL | 4.9214 mL |
| 50 mM | 0.0394 mL | 0.1969 mL | 0.3937 mL | 0.7874 mL | 0.9843 mL |
| 100 mM | 0.0197 mL | 0.0984 mL | 0.1969 mL | 0.3937 mL | 0.4921 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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MK-8033 hydrochloride is a specific dual inhibitor of c-Met/Ron with the IC50 value of 1.3nM for c-Met [1].
MK-8033 hydrochloride has been reported to potently inhibit c-Met/HGF-dependent cellular phenotypes in vitro. The studies shown that MK-8033 inhibit the phosphorylation of Y1349 of c-Met with the IC50 value of 0.03μM and proliferation with the IC50 value of 0.58μM in the GTL-16 cell lines. In addition, MK-8033 hydrochloride has also been revealed to preferentially bind to and inhibit the catalytic activity of activated c-Met kinase. Furthermore, MK-8033 hydrochloride has been noted to bind 3-fold more tightly to phosphorylated counterpart with the Kd value of 10.4nM in a BIAcore-based direct binding assay. Apart from these, MK-8033 hydrochloride has shown a inhibitory effect on WT and oncogenic c-Met at 50μM ATP with the IC50 values of 1.3nM, 1.0nM, 0.6nM and 0.6nM for WT c-Met, c-Met(Y1230C), c-Met(Y1230H) and c-Met(Y1235D), respectively [1].
References:
[1] Northrup AB1, Katcher MH, Altman MD, Chenard M, Daniels MH, Deshmukh SV, Falcone D, Guerin DJ, Hatch H, Li C, Lu W, Lutterbach B, Allison TJ, Patel SB, Reilly JF, Reutershan M, Rickert KW, Rosenstein C, Soisson SM, Szewczak AA, Walker D, Wilson K, Young JR, Pan BS, Dinsmore CJ. 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. doi: 10.1021/jm301619u. Epub 2013 Mar 18.
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