| Identification | Back Directory | [Name]
ALR-3456 | [CAS]
845256-65-7 | [Synonyms]
MK0731
ALR-3456
MK0731,MK 0731
ALR-3456 , MK-0731
(R)-2-aMino-2-cyclopropyl-1-((S)-4-(2,5-difluorophenyl)-2-phenyl-2H-pyrrol-1(5H)-yl)ethanone
(5S)-3-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-(hydroxymethyl)-N-methyl-5-phenyl-2H-pyrrole-1-carboxamide
(S)-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
(2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methyl-4-piperidinyl]-2,5-dihydro-2-(hydroxymethyl)-N-methyl-2-phenyl-1H-pyrrole-1-carboxamide
1H-Pyrrole-1-carboxamide, 4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methyl-4-piperidinyl]-2,5-dihydro-2-(hydroxymethyl)-N-methyl-2-phenyl-, (2S)- | [Molecular Formula]
C25H28F3N3O2 | [MDL Number]
MFCD11977272 | [MOL File]
845256-65-7.mol | [Molecular Weight]
459.509 |
| Chemical Properties | Back Directory | [Boiling point ]
590.5±50.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
14.57±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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[1][2]. | [in vivo]
MK-0731 (40 mg/kg/day; sc; for 11 days) inhibits the growth of KB-v tumors that highly overexpress Pgp, whereas Paclitaxel (HY-B0015) has no effect[1].
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 |
| Animal Model: | Mice for the dual flank xenograft KB-3-1 and KB-v-1 cells[1] | | Dosage: | 40 mpk | | Administration: | SC; qd×1; for 11 days | | Result: | Inhibited the growth of KB-v tumors that highly overexpress Pgp, whereas Paclitaxel (20 mpk; qd×5) had no effect.
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| [IC 50]
KSP: 2.2 nM (IC50) | [References]
[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. DOI:10.1021/jm800386y
[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. DOI:10.1007/s10637-011-9653-1 |
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| Company Name: |
NCE Biomedical Co.,Ltd.
|
| Tel: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
|