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CAS:5465-86-1
品牌:MedChemExpress (MCE)
存储条件:Pure form: -20°C, 3 years; 4°C, 2 years.In solvent: -80°C, 6 months; -20°C, 1 month.
生物活性:ML204 是一种有效的选择性 TRPC4/TRPC5 通道抑制剂,对 TRPC6 的选择性至少是 19 倍,对所有其他 TRP 通道以及电压门控钠、钾或 Ca< sup>2+ 个频道[1][2]。
体外:ML204 抑制 TRPC4β 介导的细胞内 Ca2+ 升高,IC50 值为 0.96 μM(HEK293 细胞),对毒蕈碱受体偶联的 TRPC6 通道激活具有 19 倍的选择性[1].ML204 阻断 TRPC4β 活性,该活性通过 μ-阿片类药物、5HT1A 血清素、Gi/o 刺激诱导,和 M2 毒蕈碱受体或内源性 M3 样毒蕈碱受体刺激 Gq/11[1].ML204 阻断 LPS 诱导的 TRPC5 通道活性[3]。
体内:ML204(1 毫克/千克;皮下注射;每天两次;持续 5 天)导致注射 LPS 的小鼠因体温过低加剧而死亡,并降低腹膜白细胞数量和细胞因子[4]。
参考文献:[1]. Miller M, et al. Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels. J Biol Chem. 2011 Sep 23;286(38):33436-46.[2]. Miller MR, et al. Novel Chemical Inhibitor of TRPC4 Channels. Probe Reports from the NIH Molecular Libraries Program [Internet].[3]. Thomas Schaldecker, et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J Clin Invest. 2013 Dec 2; 123(12): 5298–5309.[4]. Domingos M S Pereira, et al. Transient Receptor Potential Canonical Channels 4 and 5 Mediate Escherichia coli-Derived Thioredoxin Effects in Lipopolysaccharide-Injected Mice. Oxid Med Cell Longev. 2018 Jun 10;2018:4904696.
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