Bitopertin

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Chemical Structure| 845614-11-1 同义名 : 比拓喷丁 ;RG1678; RO4917838; R-1678
CAS号 : 845614-11-1
货号 : A514249
分子式 : C21H20F7N3O4S
纯度 : 99%
分子量 : 543.46
MDL号 : MFCD18251496
存储条件：

Pure form Inert atmosphere, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(92 mM)，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
生物活性
靶点

  • GlyT1

    GlyT1, IC50:22 nM
描述 Bitopertin is a potent and noncompetitive glycine reuptake inhibitor targeting on GlyT1 (glycine transporter type 1), with IC50 value of 25nM. Bitopertin enhanced NMDA-dependent long-term potentiation at 100 nM but not at 300 nM in hippocampal CA1 pyramidal cells. It dose-dependently increased cerebrospinal fluid and striatal levels of glycine measured by microdialysis in rats. Also, it attenuated hyperlocomotion induced by the psychostimulant D-amphetamine or the NMDA receptor glycine site antagonist L-687,414 in mice. Additionally, it prevented the hyper-response to D-amphetamine challenge in rats treated chronically with phencyclidine, an NMDA receptor open-channel blocker. Bitopertin is usually used in study of schizophrenia. It can modulate both glutamatergic and dopaminergic neurotransmission in animal experiments that model aspects of schizophrenia.
作用机制 Bitopertin could competitively block [3H]ORG24598 binding sites at human GlyT1b.[1]
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
NCT01192906 Schizophrenia Phase 3 Completed - -
NCT01234779 Schizophrenia Phase 2 Completed - -
NCT01235559 Schizophrenia Phase 3 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.84mL

0.37mL

0.18mL

9.20mL

1.84mL

0.92mL

18.40mL

3.68mL

1.84mL
参考文献

[1]Alberati D, Moreau JL, et al. Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an investigational agent for the treatment of schizophrenia. Neuropharmacology. 2012 Feb;62(2):1152-61.

[2]Bugarski-Kirola D, Wang A, et al. A phase II/III trial of bitopertin monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia - results from the CandleLyte study. Eur Neuropsychopharmacol. 2014 Jul;24(7):1024-36.

[3]Armbruster A, Neumann E, et al. The GlyT1 Inhibitor Bitopertin Ameliorates Allodynia and Hyperalgesia in Animal Models of Neuropathic and Inflammatory Pain. Front Mol Neurosci. 2018 Jan 10;10:438.

[4]Effects of Clozapine, Aripiprazole and Bitopertin in Rats Social Withdrawal Assessed in an Automatic Social Interaction Test

[5]Pinard E, Alanine A, et al. Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J Med Chem. 2010 Jun 24;53(12):4603-14.