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680C91

680C91用途

680C91是一种口服活性、选择性色氨酸2,3-双加氧酶(TDO)抑制剂,Ki为51 nM。TDO是色氨酸分解代谢的关键酶。680C91可用于癌症免疫治疗和阿尔茨海默病的研究[1][2][3][4]。

680C91名称

[ CAS 号 ]:
163239-22-3

[ 中文名 ]:
(E)-6-氟-3-(2-(吡啶-3-基)乙烯基)-1H-吲哚

[ 英文名 ]:
680C91

[英文别名 ]:

PSB 0777 ammonium salt

680C91生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 癌症

信号通路 >> 其他 >> 其他

研究领域 >> 炎症/免疫

研究领域 >> 神经疾病

[体外研究]

680C91是一种有效的(Ki=51 nM)选择性TDO抑制剂,在10μM浓度下对吲哚胺2,3-双加氧酶、单胺氧化酶a和B、5-HT摄取和5-HT1A、1D、2A和2C受体没有抑制活性[2]。680C91抑制大鼠肝细胞和原位灌流大鼠肝对色氨酸的分解代谢[2]。Tdo2可调节子宫基质细胞和蜕膜细胞的增殖,刺激蜕膜标志物Dtprp的表达。Tdo2抑制剂680C91也能在24小时内抑制子宫蜕膜细胞的增殖活性[3]。用680C91(25和50μM)处理平滑肌瘤平滑肌细胞(LSMC)和肌层平滑肌细胞(MSMC)球体,以剂量依赖性方式显著抑制I型胶原(COL1A1)和III型胶原(COL3A1)的表达[4]。细胞增殖试验[3]细胞系：子宫基质细胞浓度：0.01,0.05,0.1,0.5,1,5和10 μM培养时间：24小时结果：5小时和10小时时,基质细胞的增殖活性显著降低 μM.Western Blot分析[4]细胞系：MSMC和LSMC浓度：25和50μM培养时间：48小时结果：显著降低LSMC球体中COL1A1和COL3A1的表达,对MSMC球体中这些蛋白质的表达没有显著影响。

[体内研究]

680C91(急性治疗剂量为15 mg/kg)可提高大脑中的色氨酸[5]。动物模型：13-18周龄的雄性C57Bl6/NCrl小鼠[5]剂量：15 mg/kg给药：按os给药结果：导致大脑色氨酸显著增加。

[参考文献]

[1]. M Salter, et al. The effects of an inhibitor of tryptophan 2,3-dioxygenase and a combined inhibitor of tryptophan 2,3-dioxygenase and 5-HT reuptake in the rat. Neuropharmacology. 1995 Feb;34(2):217-27.

[2]. M Salter, et al. The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochem Pharmacol. 1995 May 17;49(10):1435-42.

[3]. Dang-Dang Li, et al. Differential expression and regulation of Tdo2 during mouse decidualization. J Endocrinol. 2013 Dec 2;220(1):73-83.

[4]. Tsai-Der Chuang, et al. Tryptophan catabolism is dysregulated in leiomyomas. Fertil Steril. 2021 Oct;116(4):1160-1171.

[5]. Sophie Imbeault, et al. Effects of IDO1 and TDO2 inhibition on cognitive deficits and anxiety following LPS-induced neuroinflammation. Acta Neuropsychiatr. 2020 Feb;32(1):43-53.

680C91物理化学性质

[ 分子式 ]:
C₁₅H₁₁FN₂

[ 分子量 ]:
238.26000

[ 精确质量 ]:
238.09100

[ PSA ]:
28.68000

[ LogP ]:
3.87240

[ 储存条件 ]:
2-8°C，密封，干燥

680C91MSDS

详细MSDS(安全技术说明书)

680C91安全信息

[ 符号 ]:

GHS05

[ 信号词 ]:
Danger

[ 危害声明 ]:
H318

[ 警示性声明 ]:
P280-P305 + P351 + P338

[ 危害码 (欧洲) ]:
C

[ 危险品运输编码 ]:
NONH for all modes of transport

680C91文献

A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer.

Cancer Res. 75 , 4651-64, (2015)

The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast ...

L-kynurenine/aryl hydrocarbon receptor pathway mediates brain damage after experimental stroke.

Circulation 130(23) , 2040-51, (2014)

Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (Per-Arnt-Sim homology domain) family known to mediate the toxic and carcinogenic effects of xe...

Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites.

.PubMed ID

Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeu...

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