Identification of Dihydroorotate Dehydrogenase Inhibitors Using the Cell Painting Assay.

ABSTRACT: Profiling approaches have been increasingly employed for the characterization of disease-relevant phenotypes or compound perturbation as they provide a broad, unbiased view on impaired cellular states. We report that morphological profiling using the cell painting assay (CPA) can detect modulators of de novo pyrimidine biosynthesis and of dihydroorotate dehydrogenase (DHODH) in particular. The CPA can differentiate between impairment of pyrimidine and folate metabolism, which both affect cellular nucleotide pools. The identified morphological signature is shared by inhibitors of DHODH and the functionally tightly coupled complex III of the mitochondrial respiratory chain as well as by UMP synthase, which is downstream of DHODH. The CPA appears to be particularly suited for the detection of

SUBMITTER: Scholermann B 

PROVIDER: S-EPMC9828254 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature