MAKOTO KAWATANI1,2,*, HARUMI AONO2, SAYOKO HIRANUMA3, TAKESHI SHIMIZU3, MAKOTO MUROI1,2, TOSHIHIKO NOGAWA4, TOMOKAZU OHISHI5, SHUN-ICHI OHBA5, MANABU KAWADA5, KANAMI YAMAZAKI6, SHINGO DAN6, NAOSHI DOHMAE1, HIROYUKI OSADA2,7,*
Oncology Research, Vol.31, No.6, pp. 833-844, 2023, DOI:10.32604/or.2023.030241
Abstract Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro, whereas NPD723 was approximately… More >
Login
Register
