| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Ron (IC50 = 27 nM)
MK8033 HCl targets c-Met and Ron, receptor tyrosine kinases that are involved in cell proliferation, survival, motility, and angiogenesis. The compound is a dual inhibitor of c-Met and Ron, with an IC50 of 1 nM for wild-type c-Met. MK8033 binds 3-fold more tightly to the phosphorylated c-Met kinase domain (Kd = 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). By inhibiting c-Met and Ron, the compound blocks downstream signaling pathways involved in tumor growth and metastasis. |
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| ln Vitro |
MK-8033 (Compound 11r, 10 μM) showed a 31% CYP3A4 (cytochrome P450 3A4) inhibition[1].
MK-8033 (1 μM, 2 h) inhibits the c-Met-dependent gastric cancer cell line GTL-16's Y1349 phosphorylation (IC50: 0.03 μM)[1]. MK-8033 (1-10 μM, 72 h) suppresses the growth of GTL-16 cells (IC50: 0.58 μM)[1]. MK-8033 inhibits oncogenic c-Met activation loop mutants with IC50s ranging from 0.6 to 1 nM. It binds more tightly to phosphorylated c-Met (Kd: 3.2 nM) than to its unphosphorylated counterpart (Kd: 10.4 nM).[1] MK-8033 (0.1-10 μM, 2 h) decreases c-Met, ERK, and Akt phosphorylation in EBC-1 and H1993 cells[2]. MK-8033 (1 μM, 1 h) increases the radiation sensitivity of high c-Met-expressing H1993 and EBC-1 cells[2]. MK-8033 (10 μM, 6 h) reduces DNA repair and increases γ-H2Ax levels in comparison to double irradiation in A549 cells[2]. MK-8033 (2 μM, 72 h) causes G-alpha protein mutant UM (uveal melanoma) cells to proliferate less, but induces apoptosis somewhat[3]. In vitro, MK8033 HCl demonstrates potent inhibition of c-Met with an IC50 of 1 nM for wild-type c-Met. The compound shows 3-fold higher binding affinity for the phosphorylated c-Met kinase domain (Kd = 3.2 nM) compared to the unphosphorylated form (Kd = 10.4 nM). MK8033 reduces the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells. Specific cellular proliferation IC50 values are not detailed in the available sources. The compound is selective for c-Met and Ron. |
| ln 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 shows good bioavailability (35% for rats, 33% for dogs) and moderate clearance (t1/2: 0.8 h for rats, 3.1 h for dogs)[1]. Specific in vivo activity data for MK8033 HCl are not detailed in the available sources. As an orally bioavailable c-Met/Ron inhibitor, the compound is expected to have antitumor activity in vivo. It is under investigation as a treatment for cancer, including breast cancer, bladder cancer, and NSCLC. Specific animal model studies (such as xenograft models) have not been described in the available literature. The compound is intended for research use only. |
| Enzyme Assay |
The c-Met kinase inhibition assay for MK8033 HCl involves incubating the compound with recombinant c-Met kinase, ATP, and a peptide substrate. The reaction is carried out in a kinase buffer optimized for c-Met activity. After incubation, the amount of phosphorylated substrate is quantified using a luminescence-based kinase assay. IC50 values are calculated from dose-response curves. Binding affinity can be assessed using surface plasmon resonance (SPR) to determine Kd values for both phosphorylated and unphosphorylated c-Met.
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| Cell Assay |
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. To evaluate the cellular activity of MK8033 HCl, cancer cells that express c-Met (such as A549 lung cancer cells) are seeded in 96-well plates and treated with varying concentrations of MK8033 HCl. After 72 hours of incubation, cell proliferation is measured using an MTT or SRB assay. The compound's effect on c-Met signaling is assessed by measuring c-Met phosphorylation and downstream signaling targets using Western blot analysis. The effect of radiation-induced c-Met activation can also be assessed. Apoptosis induction can be evaluated using annexin V-FITC staining and flow cytometry. |
| Animal Protocol |
Human GTL-16 c-Met amplified gastric tumor xenografts
3, 10, 30, and 100 mg/kg Oral administration, twice daily for 21 days Specific in vivo animal experiment protocols for MK8033 HCl are not detailed in the available sources. As a c-Met/Ron inhibitor, the compound would typically be evaluated in xenograft models using human cancer cell lines that express c-Met or Ron. Immunodeficient mice would be implanted with tumor cells subcutaneously, and MK8033 HCl would be administered orally at various doses once tumors reach a certain size. Tumor growth inhibition would be measured over the treatment period. However, specific protocols are not described in the available literature. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for MK8033 HCl are not provided in the available sources. The compound is a small molecule with a molecular weight of 507.99 and a molecular formula of C25H22ClN5O3S. As an orally bioavailable compound, it is expected to have favorable absorption properties. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS to determine key PK parameters.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK8033 HCl are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is available with a purity of ≥98%. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment.
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| References |
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| Additional Infomation |
MK8033 HCl is a novel, potent, selective, ATP-competitive small-molecule dual inhibitor of c-Met and Ron with an IC50 of 1 nM for wild-type c-Met. It binds 3-fold more tightly to the phosphorylated c-Met kinase domain (Kd = 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). It is under investigation as a treatment for cancer, including breast cancer, bladder cancer, and NSCLC. The compound reduces radiation-induced phosphorylated c-Met in A549 cells.
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| Molecular Formula |
C25H22CLN5O3S
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|---|---|
| Molecular Weight |
507.991882801056
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| Exact Mass |
507.113
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| CAS # |
1283000-43-0
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| Related CAS # |
MK-8033;1001917-37-8
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| PubChem CID |
51030992
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| Appearance |
Light yellow to yellow solid
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| LogP |
5.437
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
859
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(CC1=CC=C2C(C(C3=CC(C4=CN(C)N=C4)=CN=C3C=C2)=O)=C1)(NCC5=NC=CC=C5)=O.Cl
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| InChi Key |
BKIQDRGTLKPYCL-UHFFFAOYSA-N
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| InChi Code |
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
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| Chemical Name |
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;hydrochloride
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| Synonyms |
MK-8033; MK8033; MK 8033; MK-8033 hydrochloride; MK8033 HCL
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: ~7.1 mg/mL (~14.1 mM)
DMSO: ~5.9 mg/mL (~11.6 mM） |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.59 mg/mL (1.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.9 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.59 mg/mL (1.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.9 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9685 mL | 9.8427 mL | 19.6854 mL | |
| 5 mM | 0.3937 mL | 1.9685 mL | 3.9371 mL | |
| 10 mM | 0.1969 mL | 0.9843 mL | 1.9685 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
MK-8033 affects c-Met–induced signaling in EBC-1 and H1993 cells but not in A549 and H460 cells.
Radiation induces c-Met expression and radiosensitizes A549 and H460 cells. |
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MK-8033 radiosensitizes EBC-1 and H1993 cells but not A549 and H460 NSCLC cells. A 1-hour pretreatment with MK-8033 (1 μM) radiosensitized NSCLC cells with high basal c-Met levels (EBC-1 and H1993) but not in low c-Met-expressing cells.J Thorac Oncol.2012 Aug;7(8):1211-7. |
A, MK-8033 reduces p-c-Met levels in A549 cells after radiation. A single dose of radiation did not affect the expression of phosphorylated (activated) c-Met, but fractionated radiation (i.e., two doses) did. This increase was attenuated by the addition of MK-8033 (10μM, 2 hours after first radiation) between the two radiation doses.J Thorac Oncol.2012 Aug;7(8):1211-7. |
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