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Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation.
Dorel R,
Sun D,
Carruthers N,
Castanedo GM,
Ung PM,
Factor DC,
Li T,
Baumann H,
Janota D,
Pang J,
Salphati L,
Meklemburg R,
Korman AJ,
Harper HE,
Stubblefield S,
Payandeh J,
McHugh D,
Lang BT,
Tesar PJ,
Dere E,
Masureel M,
Adams DJ,
Volgraf M,
Braun MG
J Med Chem 67 4819-4832 (2024)
Abstract
The inhibition of emopamil binding protein (EBP), a sterol isomerase within the cholesterol biosynthesis pathway, promotes oligodendrocyte formation, which has been proposed as a potential therapeutic approach for treating multiple sclerosis. Herein, we describe the discovery and optimization of brain-penetrant, orally bioavailable inhibitors of EBP. A structure-based drug design approach from literature compound
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