| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Ron (IC50 = 7 nM)
MK8033 targets c-Met, a receptor tyrosine kinase that is activated by hepatocyte growth factor (HGF). c-Met signaling plays a critical role in cell proliferation, survival, motility, and angiogenesis. Overexpression or constitutive activation of c-Met is associated with tumor growth, invasion, and metastasis in various cancers. By inhibiting c-Met, MK8033 blocks downstream signaling pathways and may induce cell death in tumor cells. The compound is a potent, orally bioavailable small-molecule inhibitor of c-Met. |
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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 demonstrates potent inhibition of c-Met kinase activity. The compound is a c-Met inhibitor with potential antineoplastic activity. It binds to and inhibits c-Met, thereby blocking downstream signal transduction pathways. Specific IC50 values for inhibition of c-Met or cellular proliferation are not detailed in the available sources. MK8033 has been shown to induce cell death in tumor cells overexpressing or expressing constitutively activated c-Met protein. |
| 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 are not detailed in the available sources. As an orally bioavailable c-Met inhibitor, the compound is expected to have antitumor activity in vivo. MK8033 has potential antineoplastic activity and may induce cell death in tumor cells overexpressing or expressing constitutively activated c-Met protein. 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 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 (such as ADP-Glo) or a radiometric assay. IC50 values are calculated from dose-response curves. The compound's binding affinity for c-Met can be assessed using surface plasmon resonance (SPR) or other binding assays.
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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, cancer cells that express c-Met (such as A549 lung cancer cells, which express constitutively activated c-Met) are seeded in 96-well plates and treated with varying concentrations of MK8033. 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 (such as AKT and ERK) using Western blot analysis. 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 are not detailed in the available sources. As a c-Met inhibitor, the compound would typically be evaluated in xenograft models using human cancer cell lines that overexpress c-Met. Immunodeficient mice would be implanted with tumor cells subcutaneously, and MK8033 would be administered orally at various doses once the 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 |
MK8033 is characterized as being orally bioavailable. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 471.53 and a molecular formula of C25H21N5O3S. It is a small molecule with properties suitable for oral administration. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK8033 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 |
The c-Met inhibitor MK8033 is an orally bioavailable c-Met inhibitor with potential antitumor activity. After administration, MK8033 binds to the c-Met protein and inhibits its autophosphorylation, thereby disrupting the c-Met signaling pathway and potentially inducing death in tumor cells that overexpress or constitutively activate c-Met protein. Furthermore, MK8033 also inhibits Ron (a receptor derived from Nantes, MST1R). The c-Met protein, encoded by the proto-oncogene MET, is a receptor tyrosine kinase, also known as the hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in various tumor cell types and plays a crucial role in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. Ron is a member of the Met family of cell surface receptor tyrosine kinases and is also overexpressed in certain tumor cell types.
MK8033 is an orally bioavailable inhibitor of c-Met, a receptor tyrosine kinase involved in cell proliferation, survival, motility, and angiogenesis. It has potential antineoplastic activity and may induce cell death in tumor cells overexpressing or expressing constitutively activated c-Met protein. The compound has a molecular formula of C25H21N5O3S and a molecular weight of 471.53. It is supplied for research purposes with a purity of ≥98%. |
| Molecular Formula |
C25H21N5O3S
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|---|---|
| Molecular Weight |
471.53094
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| Exact Mass |
471.137
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| Elemental Analysis |
C, 63.68; H, 4.49; N, 14.85; O, 10.18; S, 6.80
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| CAS # |
1001917-37-8
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| Related CAS # |
MK-8033 hydrochloride;1283000-43-0
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| PubChem CID |
45142457
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.39
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| LogP |
4.635
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
859
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(NCC1=CC=CC=N1)(CC2=CC=C3C(C(C4=CC(C5=CN(N=C5)C)=CN=C4C=C3)=O)=C2)=O
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| InChi Key |
VMJFTOSOFDEKTM-UHFFFAOYSA-N
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| InChi Code |
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
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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
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| Synonyms |
MK-8033; MK8033; MK 8033
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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 |
| 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) |
DMSO: ≥ 46 mg/mL (~97.6 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.12 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 10.0 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: ≥ 1 mg/mL (2.12 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 10.0 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 | 2.1208 mL | 10.6038 mL | 21.2076 mL | |
| 5 mM | 0.4242 mL | 2.1208 mL | 4.2415 mL | |
| 10 mM | 0.2121 mL | 1.0604 mL | 2.1208 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00559182 | Completed | Drug: Comparator: MK-8033 Drug: Comparator: MK-8033 +/- omeprazole |
Advanced Cancer | Merck Sharp & Dohme LLC | December 5, 2007 | Phase 1 |
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