Dataset Information

Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.

ABSTRACT: Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally, these compounds had low P-gp efflux ratios, allowing for applications where exposure to the brain would be required.

SUBMITTER: DeRatt LG

PROVIDER: S-EPMC10945543 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.

DeRatt Lindsey G LG Pietsch E Christine EC Cisar Justin S JS Jacoby Edgar E Kazmi Faraz F Matico Rosalie R Shaffer Paul P Tanner Alexandra A Wang Weixue W Attar Ricardo R Edwards James P JP Kuduk Scott D SD

ACS medicinal chemistry letters 20240207 3

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally ...[more]

PMID: 38505861

Dataset Information

Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.

Publications

Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.

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