Bitopertin
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Bitopertin,亦称RG1678,是有效的GlyT1选择性抑制剂,其EC50值为30 nM[1]。
N-甲基-D-天冬氨酸(NMDA)受体介导的异常信号传导是多种精神分裂症体征和症状的关键成因。NMDA受体功能亢进可以缓解受体信号传导功能紊乱,有望用于精神分裂症治疗。靶向NMDA受体别构甘氨酸位点可以增强NMDA受体功能,从而恢复正常的谷氨酸传递。此效果可以通过甘氨酸激动剂和通过抑制甘氨酸转运蛋白1(GlyT1)阻止突触间的甘氨酸清除来实现。Bitopertin选择性抑制GlyT1,从而增加甘氨酸(NMDA受体的协同激动剂)在突触间的数量,最终增强NMDA信号传导[1,2]。
据发现,Bitopertin具有较高的GlyT1体外抑制活性,其EC50值为30 nM,同时,也具有较高的hERG活性,其IC50为17 μM。此外,与GlyT2和其它86个靶点(包括跨膜和可溶性受体、酶、离子通道和单胺转运体)相比,Bitopertin对GlyT1具有非常高的选择性。尽管Bitopertin显示出较低的水溶性,它在禁食状态下的模拟肠液(20 μg/mL)和进食状态下的模拟肠液(60 μg/mL)中显示出良好的溶解性。此外,在平行人工膜渗透性试验中,Bitopertin显示出很好的膜通透性[1]。
在II期RCT研究中,将安慰剂和不同剂量的Bitopertin加入到传统的抗精神病药物治疗中,持续8周。结果表明,Bitopertin组具有显著更高的应答率和功能改善趋势。Bitopertin抑制甘氨酸摄取的功效有望用于治疗精神分裂症阴性症状[2]。
参考文献:
1. Pinard E, Alanine A, Alberati D, 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]. Journal of medicinal chemistry, 2010, 53(12): 4603-4614.
2. Umbricht D, Alberati D, Martin-Facklam M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study[J]. JAMA psychiatry, 2014.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 543.46 |
Cas No. | 845614-11-1 |
Formula | C21H20F7N3O4S |
Synonyms | RG1678;RO4917838;RG-1678;RG 1678;RO-4917838;RO 4917838 |
Solubility | insoluble in H2O; ≥17.94 mg/mL in EtOH; ≥88.9 mg/mL in DMSO with ultrasonic |
Chemical Name | [4-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]-[5-methylsulfonyl-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxyphenyl]methanone |
SDF | Download SDF |
Canonical SMILES | CC(C(F)(F)F)OC1=C(C=C(C=C1)S(=O)(=O)C)C(=O)N2CCN(CC2)C3=C(C=C(C=N3)C(F)(F)F)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |