845256-65-7
845256-65-7 structure
- Name: MK0731
- Chemical Name: (R)-2-aMino-2-cyclopropyl-1-((S)-4-(2,5-difluorophenyl)-2-phenyl-2H-pyrrol-1(5H)-yl)ethanone
- CAS Number: 845256-65-7
- Molecular Formula: C25H28F3N3O2
- Molecular Weight: 459.504
- Catalog: Signaling Pathways Apoptosis Apoptosis
- Create Date: 2018-12-18 20:26:33
- Modify Date: 2024-01-14 19:17:27
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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].
| Name | (R)-2-aMino-2-cyclopropyl-1-((S)-4-(2,5-difluorophenyl)-2-phenyl-2H-pyrrol-1(5H)-yl)ethanone |
|---|---|
| Synonyms |
(2S)-4-(2,5-Difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methyl-4-piperidinyl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-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)- 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) ALR-3456,MK-0731 (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 MK0731 MFCD11977272 |
| Description | 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]. |
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| Related Catalog | |
| Target |
KSP:2.2 nM (IC50) |
| In Vitro | MK-0731 (0.415-300 nM; 48 小时) 诱导 A2780 细胞凋亡，EC50 为 2.7 nM[1]。 MK-0731 对结合 hERG 通道的亲和力很小 (IC50=20.5 μM)[1]。 MK-0731 能够在细胞中诱导有丝分裂阻滞，IC50 为 19 nM[1]。 Apoptosis Analysis[1] Cell Line: A2780 cells Concentration: 0.415-300 nM Incubation Time: 48 h Result: Induced apoptosis with an EC50 of 2.7 nM. |
| In Vivo | MK-0731 (40 mg/kg/天; 皮下注射; 持续 11 天) 抑制高度过表达 Pgp 的 KB-v 肿瘤的生长，而紫杉醇 (HY-B0015) 没有作用[1]。 MK-0731 (2.5, 5, 10, 20, 40 mg/kg/天; 微型泵) 在 A2780 异种移植小鼠的肿瘤暴露和有丝分裂停滞方面表现出与剂量成比例的增加[1]。 MK-0731 (1 mg/kg/天; 静脉给药) 对于大鼠的 T1/2 为 1 小时，CL 为 66 mL/min•kg，Vss 3 L/kg[1]。 Pharmacokinetic Parameters of MK-0731[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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 590.5±50.0 °C at 760 mmHg |
| Molecular Formula | C25H28F3N3O2 |
| Molecular Weight | 459.504 |
| Flash Point | 310.9±30.1 °C |
| Exact Mass | 459.213348 |
| PSA | 47.02000 |
| LogP | 3.61 |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.615 |