MAKOTO KAWATANI^1,2,*, HARUMI AONO², SAYOKO HIRANUMA³, TAKESHI SHIMIZU³, MAKOTO MUROI^1,2, TOSHIHIKO NOGAWA⁴, TOMOKAZU OHISHI⁵, SHUN-ICHI OHBA⁵, MANABU KAWADA⁵, KANAMI YAMAZAKI⁶, SHINGO DAN⁶, NAOSHI DOHMAE¹, HIROYUKI OSADA^2,7,*

Oncology Research, Vol.31, No.6, pp. 833-844, 2023, DOI:10.32604/or.2023.030241 - 15 September 2023

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 More >

PRIYANKA SOLANKI¹, NISARG RANA¹, PRAKASH C. JHA², ANU MANHAS^1,*

BIOCELL, Vol.47, No.4, pp. 707-729, 2023, DOI:10.32604/biocell.2023.026615 - 08 March 2023

Abstract Cancer is considered one of the most lethal diseases responsible for causing deaths worldwide. Although there have been many breakthroughs in anticancer development, cancer remains the major cause of death globally. In this regard, targeting cancer-causing enzymes is one of the efficient therapeutic strategies. Biological functions like cell cycle, transcription, metabolism, apoptosis, and other depend primarily on cyclin-dependent kinases (CDKs). These enzymes help in the replication of DNA in the normal cell cycle process, and deregulation in the functioning of any CDK can cause abnormal cell growth, which leads to cancer. This review is focused More >