|3-(9-(叔丁基)-8-((1-甲基-1H-1,2,4-三唑-5-基)甲氧基)吡唑并[1,5-d][1,2,4]三嗪-2-基)-5-甲基异恶唑|CsnPharm

CAS No.: 342652-67-9

MRK-016 Catalog No. CSN18228

Synonyms: Mrk-016

MRK-016 is a functionally selective, inverse agonist at the benzodiazepine site of GABAA α5 receptors.

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靶点选择性

生物活性

实验方案

技术信息

生物活性

描述MRK-016 is a pyrazolotriazine with an affinity of between 0.8 and 1.5 nM for the benzodiazepine binding site of native rat brain and recombinant human alpha1-, alpha2-, alpha3-, and alpha5-containing GABA(A) receptors. It has inverse agonist efficacy selective for the alpha5 subtype. MRK-016 gave good receptor occupancy after oral dosing in rats, with the dose required to produce 50% occupancy being 0.39 mg/kg and a corresponding rat plasma EC(50) value of 15 ng/ml that was similar to the rhesus monkey plasma EC(50) value of 21 ng/ml obtained using [(11)C]flumazenil positron emission tomography. In normal rats, MRK-016 enhanced cognitive performance in the delayed matching-to-position version of the Morris water maze but was not anxiogenic, and in mice it was not proconvulsant and did not produce kindling. MRK-016 had a short half-life in rat, dog, and rhesus monkey (0.3-0.5 h) but had a much lower rate of turnover in human compared with rat, dog, or rhesus monkey hepatocytes^[3]. MRK (MRK-016) can prevent LPS- induced cognitive deficits associated with elevated Aβ, and restore hippocampal BDNF expression^[4].
参考文献

[1] Eimerbrink MJ, White JD, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res. 2015 Jul 15;288:50-3.
[2] Atack JR, Maubach KA, et al. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)- pyrazolo[1,5-d] -[1,2,4] triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84.
[3] Atack JR, Maubach KA, Wafford KA, O'Connor D, Rodrigues AD, Evans DC, Tattersall FD, Chambers MS, MacLeod AM, Eng WS, Ryan C, Hostetler E, Sanabria SM, Gibson RE, Krause S, Burns HD, Hargreaves RJ, Agrawal NG, McKernan RM, Murphy MG, Gingrich K, Dawson GR, Musson DG, Petty KJ. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84
[4] Eimerbrink MJ, Pendry RJ, Hodges SL, Wiles JD, Peterman JL, White JD, Hayes HB, Chumley MJ, Boehm GW. The α5-GABAAR inverse agonist MRK-016 upregulates hippocampal BDNF expression and prevents cognitive deficits in LPS-treated mice, despite elevations in hippocampal Aβ. Behav Brain Res. 2019 Feb 1;359:871-877

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.7145 mL
- 13.5725 mL
- 27.1449 mL
- 5 mM
- 0.5429 mL
- 2.7145 mL
- 5.4290 mL
- 10 mM
- 0.2714 mL
- 1.3572 mL
- 2.7145 mL

技术信息

CAS号

342652-67-9

储存条件

粉末: Inert atmosphere,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C17H20N8O2

运输

蓝冰

分子量

368.39

别名

Mrk-016

溶解度

DMSO	50.0 mg/mL (135.7 mM) warming

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