Identification of Dihydroorotate Dehydrogenase Inhibitors─Indoluidins─That Inhibit Cancer Cell Growth.
Animals
Antineoplastic Agents
/ chemistry
Cell Differentiation
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Databases, Protein
Dihydroorotate Dehydrogenase
/ antagonists & inhibitors
Enzyme Inhibitors
/ chemistry
Humans
Mice
Proteomics
Stereoisomerism
Xenograft Model Antitumor Assays
Journal
ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906
Informations de publication
Date de publication:
19 11 2021
19 11 2021
Historique:
pubmed:
4
11
2021
medline:
1
2
2022
entrez:
3
11
2021
Statut:
ppublish
Résumé
Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in de novo pyrimidine biosynthesis and is a promising cancer treatment target. This study reports the identification of indoluidin D and its derivatives as inhibitors of DHODH. Cell-based phenotypic screening revealed that indoluidin D promoted myeloid differentiation and inhibited the proliferation of acute promyelocytic leukemia HL-60 cells. Indoluidin D also suppressed cell growth in various other types of cancer cells. Cancer cell sensitivity profiling with JFCR39 and proteomic profiling with ChemProteoBase revealed that indoluidin D is a DHODH inhibitor. Indoluidin D inhibited human DHODH activity in vitro
Identifiants
pubmed: 34730931
doi: 10.1021/acschembio.1c00625
doi:
Substances chimiques
Antineoplastic Agents
0
Dihydroorotate Dehydrogenase
0
Enzyme Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM