中文名 | ML380 |
英文名 | ML380 |
别名 | 化合物ML380 |
英文别名 | ML380 ML380 ML-380 ML 380 N-ethyl-1-(1H-indazol-5-ylsulfonyl)-N-[[2-(trifluoromethyl)phenyl]methyl]piperidine-4-carboxamide |
CAS | 1627138-52-6 |
化学式 | C23H25F3N4O3S |
分子量 | 494.5298096 |
溶解度 | 溶于DMSO |
存储条件 | -20℃ |
靶点 | IC50: 190 nM (hM5), 610 nM (rM5) |
体外研究 | ML380 (0.01 nM-100 μM) robustly stimulates inositol phosphate (IP) accumulation and Ca 2+ mobilization in CHO-hM 5 cells, with pEC 50 s of 5.33 and 5.71, respectively. ML380 (0.01-30 μM) increases the ACh-stimulated IP accumulation and Ca 2+ mobilization in CHO-hM 5 cells. |
体内研究 | ML380 (1 mg/kg; i.v.) displays high clearance (66 mL/min/kg), a moderate volume of distribution (1.6 L/kg), and a short half-life (t 1/2 , 22 min) in rats. |
参考资料 展开查看 | 1: Berizzi AE, Gentry PR, Rueda P, Den Hoedt S, Sexton PM, Langmead CJ, Christopoulos A. Molecular Mechanisms of Action of M5 Muscarinic Acetylcholine Receptor Allosteric Modulators. Mol Pharmacol. 2016 Oct;90(4):427-36. doi: 10.1124/mol.116.104182. PubMed PMID: 27461343. 2: Gentry PR, Kokubo M, Bridges TM, Daniels JS, Niswender CM, Smith E, Chase P, Hodder PS, Rosen H, Conn PJ, Engers J, Brewer KA, Lindsley CW, Wood MR. Development of the First CNS penetrant M5 Positive Allosteric Modulator (PAM) Based on a Novel, non-Isatin Core. 2013 Dec 15 [updated 2015 Feb 11]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK280054/ PubMed PMID: 25834908. 3: Gentry PR, Kokubo M, Bridges TM, Noetzel MJ, Cho HP, Lamsal A, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4- carboxamide (ML380). J Med Chem. 2014 Sep 25;57(18):7804-10. doi: 10.1021/jm500995y. PubMed PMID: 25147929; PubMed Central PMCID: PMC4175000. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.022 ml | 10.111 ml | 20.221 ml |
5 mM | 0.404 ml | 2.022 ml | 4.044 ml |
10 mM | 0.202 ml | 1.011 ml | 2.022 ml |
5 mM | 0.04 ml | 0.202 ml | 0.404 ml |