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Betrixaban

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Chemical Structure| 330942-05-7 同义名 : PRT054021;MK-4448;MLN1021
CAS号 : 330942-05-7
货号 : A463156
分子式 : C23H22ClN5O3
纯度 : 99%+
分子量 : 451.906
MDL号 : MFCD16038040
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(55.32 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Serine protease factor Xa (fXa), positioned at the juncture of the intrinsic and the extrinsic pathways, play a pivotal role in the blood coagulation cascade [3]. Betrixaban is a highly potent, selective, and orally efficacious fXa inhibitor with IC50of 1.5 nM. In patch clamp hERG (human ether-a-go-go related gene) assays, Betrixaban has IC50 value of 8.9 μM. The plasma kallikrein IC50 and Ki values for Betrixaban are 6.3 μM and 3.5 μM respectively. Betrixaban (hERG Ki 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG Ki⩽0.5 μM) [3]. Dosed at 0.5 mg/kg IV and 2.5 mg/kg PO, Betrixaban has bioavailability of 51.6% in dog; dosed at 0.75 mg/kg IV and 7.5 mg/kg PO, Betrixaban has bioavailability of 58.7% in monkey [3]. After i.v. infusion for 30 min, the total plasma concentration of Betrixaban is 0.2±0.01 μM, and the percentage of unbound inhibitor is 40%±7.2% [4].
作用机制 The chloropyridine A ring extents into the fXa S1 site with the chloro atom positioned above the phenyl ring of Tyr228 and occupies a hydrophobic pocket formed by Ala190, Val213 and Tyr228.
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03728166 Venous Thromboembolism Phase 4 Not yet recruiting February 1, 2021 -
NCT03397888 Hepatic Impairment Phase 1 Completed - United States, Florida ... 展开 >> Clinical Pharmacology of Miami Hialeah, Florida, United States, 33014 收起 <<
NCT03613402 - Suspended(Due to slow enrollme... 展开 >>nt.) 收起 << January 2020 United States, North Carolina ... 展开 >> Durham Durham, North Carolina, United States, 27705 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.21mL

0.44mL

0.22mL

11.06mL

2.21mL

1.11mL

22.13mL

4.43mL

2.21mL
参考文献

[1]Lu G, DeGuzman FR, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013 Apr;19(4):446-51.

[2]Zhang P, Huang W, et al. Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenz amide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2179-85.

[3]Zhang P, Huang W, Wang L, Bao L, Jia ZJ, Bauer SM, Goldman EA, Probst GD, Song Y, Su T, Fan J, Wu Y, Li W, Woolfrey J, Sinha U, Wong PW, Edwards ST, Arfsten AE, Clizbe LA, Kanter J, Pandey A, Park G, Hutchaleelaha A, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu BY. Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2179-85. doi: 10.1016/j.bmcl.2009.02.111. Epub 2009 Mar 3. PMID: 19297154.

[4]Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Sinha U. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013 Apr;19(4):446-51. doi: 10.1038/nm.3102. Epub 2013 Mar 3. PMID: 23455714.