SAR studies toward discovery of emvododstat (PTC299), a potent dihydroorotate dehydrogenase (DHODH) inhibitor.
Eur J Med Chem
; 244: 114826, 2022 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-36242990
ABSTRACT
Dihydroorotate dehydrogenase (DHODH) is the enzyme that catalyzes a rate-determining step during the de novo synthesis of uridine, an important source of cellular pyrimidine nucleotides. Ability to modulate the activity of this enzyme may be used to control diseases associated with rapid, out-of-control cell growth in oncology, immunology, and virology. Emvododstat (PTC299) is a tetrahydro-ß-carboline DHODH inhibitor discovered through the GEMS technology (Gene Expression Modulation by Small-Molecules). Described in this paper is the lead optimization campaign that culminated in the discovery of this highly potent DHODH inhibitor.
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Base de dados:
MEDLINE
Assunto principal:
Oxirredutases atuantes sobre Doadores de Grupo CH-CH
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article