MK-0731
Based on 1 Customer Validation
MK-0731 is a selective, non-competitive and allosteric kinesin spindle protein (KSP) inhibitor with an IC50 of 2.2 nM and a pKa of 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and induces apoptosis in tumors. MK-0731 provides significant antitumor efficacy.
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- Reinheit: 99.85%
- CAS. Nr.: 845256-65-7
- Formel: C25H28F3N3O2
- Molecular Weight:459.50
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Speicherung:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
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Biologische Aktivität
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KSP 2.2 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2780 | EC50 |
5.3 nM
Compound: 30, MK-0731
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Induction of mitotic arrest in human A2780 cells expressing MDR1 after 16 hrs
Induction of mitotic arrest in human A2780 cells expressing MDR1 after 16 hrs
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[PMID: 18578472] |
| HEL | IC50 |
20.5 μM
Compound: 30, MK-0731
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Displacement of [35S]MK499 from human ERG expressed in HEL cells
Displacement of [35S]MK499 from human ERG expressed in HEL cells
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[PMID: 18578472] |
MK-0731 (0.415-300 nM; 48 h) induces apoptosis in A2780 cells with an EC50 of 2.7 nM[1].
MK-0731 displays little affinity for binding to the hERG channel (IC50=20.5 μM)[1].
MK-0731 has the ability to induce a mitotic block with an IC50 of 19 nM in cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A2780 cells
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Concentration:0.415-300 nM
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Incubation Time:48 h
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Result:Induced apoptosis with an EC50 of 2.7 nM.
MK-0731 (2.5, 5, 10, 20, and 40 mg/kg/day; minipump) exhibits a dose-proportional increase in both exposure and mitotic arrest in tumors in A2780-xenografted mice[1].
MK-0731 (1 mg/kg/day; iv) has a T1/2 of 1 hours, a CL of 66 mL/min•kg, and a Vss of 3 L/kg for rats[1].
Pharmacokinetic Parameters of MK-0731 in rats[1].
| rat iv (1 mg/kg) | dog iv (0.4 mg/kg) | rhesus iv (0.4 mg/kg) | |
| T1/2 (h) | 1 | 2 | 1 |
| CL (mL/min/kg) | 66.7 | 15.1 | 23.1 |
| Vss (L/kg) | 3.0 | 1.6 | 2.3 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice for the dual flank xenograft KB-3-1 and KB-v-1 cells[1]
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Dosage:40 mpk
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Administration:SC; qd×1; for 11 days
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Result:Inhibited the growth of KB-v tumors that highly overexpress Pgp, whereas Paclitaxel (20 mpk; qd×5) had no effect.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS. Nr. 845256-65-7
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Appearance Solid
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Molecular Weight 459.50
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Formel C25H28F3N3O2
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Color White to off-white
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SMILES
O=C(N(C)[C@@H](CC1)[C@H](F)CN1C)N2[C@@](C3=CC=CC=C3)(CO)C=C(C4=CC(F)=CC=C4F)C2
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
DMSO : 50 mg/mL (108.81 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
The following protocol is derived from the literature and is for reference only. It is recommended to first try a small sample.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
Reinheit & Dokumentation
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Data Sheet (281 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Christopher D Cox, et al. Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-n-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer. J Med Chem. 2008 Jul 24;51(14):4239-52. [Content Brief]
[2]. Kyle Holen, et al. A phase I trial of MK-0731, a kinesin spindle protein (KSP) inhibitor, in patients with solid tumors. Invest New Drugs. 2012 Jun;30(3):1088-95. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1763 mL | 10.8814 mL | 21.7628 mL | 54.4070 mL |
| 5 mM | 0.4353 mL | 2.1763 mL | 4.3526 mL | 10.8814 mL | |
| 10 mM | 0.2176 mL | 1.0881 mL | 2.1763 mL | 5.4407 mL | |
| 15 mM | 0.1451 mL | 0.7254 mL | 1.4509 mL | 3.6271 mL | |
| 20 mM | 0.1088 mL | 0.5441 mL | 1.0881 mL | 2.7203 mL | |
| 25 mM | 0.0871 mL | 0.4353 mL | 0.8705 mL | 2.1763 mL | |
| 30 mM | 0.0725 mL | 0.3627 mL | 0.7254 mL | 1.8136 mL | |
| 40 mM | 0.0544 mL | 0.2720 mL | 0.5441 mL | 1.3602 mL | |
| 50 mM | 0.0435 mL | 0.2176 mL | 0.4353 mL | 1.0881 mL | |
| 60 mM | 0.0363 mL | 0.1814 mL | 0.3627 mL | 0.9068 mL | |
| 80 mM | 0.0272 mL | 0.1360 mL | 0.2720 mL | 0.6801 mL | |
| 100 mM | 0.0218 mL | 0.1088 mL | 0.2176 mL | 0.5441 mL |
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