7K2U

DHODH IN COMPLEX WITH LIGAND 13

Summary for 7K2U

• Entry DOI: 10.2210/pdb7k2u/pdb
• Descriptor: Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (9 entities in total)
• Functional Keywords: dihydroorotate dehydrogenase, dhodh, oxidoreductase, inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 41956.30

Authors

Shaffer, P.L. (deposition date: 2020-09-09, release date: 2020-10-21, Last modification date: 2024-03-06)

Primary citation

DeRatt, L.G.,Christine Pietsch, E.,Tanner, A.,Shaffer, P.,Jacoby, E.,Wang, W.,Kazmi, F.,Zhang, X.,Attar, R.M.,Edwards, J.P.,Kuduk, S.D.
A carboxylic acid isostere screen of the DHODH inhibitor Brequinar.
Bioorg.Med.Chem.Lett., 30:127589-127589, 2020

PubMed Abstract: Dihydroorotate dehydrogenase (DHODH) enzymatic activity impacts many aspects critical to cell proliferation and survival. Recently, DHODH has been identified as a target for acute myeloid differentiation therapy. In preclinical models of AML, the DHODH inhibitor Brequinar (BRQ) demonstrated potent anti-leukemic activity. Herein we describe a carboxylic acid isostere study of Brequinar which revealed a more potent non-carboxylic acid derivative with improved cellular potency and good pharmacokinetic properties.

PubMed: 33007394
DOI: 10.1016/j.bmcl.2020.127589

Experimental method

X-RAY DIFFRACTION (1.73 Å)