Panarese Joseph D, Engers Darren W, Wu Yong-Jin, Bronson Joanne J, Macor John E, Chun Aspen, Rodriguez Alice L, Felts Andrew S, Engers Julie L, Loch Matthew T, Emmitte Kyle A, Castelhano Arlindo L, Kates Michael J, Nader Michael A, Jones Carrie K, Blobaum Anna L, Conn P Jeffrey, Niswender Colleen M, Hopkins Corey R, Lindsley Craig W
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.
ACS Med Chem Lett. 2018 Oct 16;10(3):255-260. doi: 10.1021/acsmedchemlett.8b00426. eCollection 2019 Mar 14.
Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive and pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.
在此，我们报告了一种新型强效、选择性、可穿透中枢神经系统且口服生物利用度高的代谢型谷氨酸受体（mGlu）正变构调节剂VU0652957（VU2957，Valiglurax）的发现。VU2957在不同物种中具有吸引人的药理和药物代谢动力学性质。为推进至临床阶段，开发了VU2957的喷雾干燥分散体（SDD）制剂，以支持开展IND启用毒理学研究。基于其整体特性，VU2957被评估为治疗帕金森病的临床前开发候选药物。
