MK-8719 is a highly potent and selective O-GlcNAcase (OGA) inhibitor (K i =7.9 nM for hOGA) with excellent CNS penetration.

2022年6月9日 · 双方成功发现了一种小分子抑制剂 MK-8719，并成功推进到临床1期实验，证明其具有良好的安全性和耐受性。目前，Alectos 已经撤回了该项目，重新开发研究新的 OGA 抑制剂项目，用于阿尔茨海默病（AD）、帕金森病（PD）、额颞叶痴呆（FTD）及相关疾病的治疗。

Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano[3,2-d]thiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human ...

SIGNIFICANCE STATEMENT: MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency.

In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These findings indicate that OGA inhibition may be a promising therapeutic strategy for the treatment of Alzheimer disease and …

2021年1月6日 · In 2019, a sugar-mimetic OGA inhibitor MK-8719, with improved pharmacokinetic profile and brain penetration, was reported as a compound to be tested in a clinical trial; however, non-sugar-like compounds with high potency and better pharmacokinetic profiles are still awaited to help characterize OGA.

MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency. In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These ...

MK-8719 | C9H14F2N2O3S | CID 136416849 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

2019年11月27日 · Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano[3,2-d]thiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human ...

MK-8719是由Alectos Therapeutics和默沙东研发的一种小分子药物，是一种OGA抑制剂。 目前该药物最高研发阶段为临床一期，用于治疗进行性核上性麻痹。 MK-8719-靶点: OGA_适应症: 进行性核上性麻痹-临床_专利_批准