Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model

Autor:	Xiangdong Liu, Andrew P. Combs, Min Wei, Changnian Liu, Peggy Scherle, Kevin Bowman, Timothy Burn, Jordan S. Fridman, Yanlong Li, Brian Wayland, Richard Wynn, Brent Douty, Holly Koblish, Brian Metcalf, Michael J. Bower, Lynn Leffet, Michael Hansbury, Qian Wang, Eddy W. Yue
Rok vydání:	2009
Předmět:	Models Molecular Amidines Molecular Conformation Pharmacology Binding Competitive HeLa chemistry.chemical_compound Inhibitory Concentration 50 Mice Non-competitive inhibition In vivo Drug Discovery Animals Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Enzyme Inhibitors Indoleamine 2 3-dioxygenase IC50 Melanoma biology Chemistry biology.organism_classification Gene Expression Regulation Neoplastic Disease Models Animal Biochemistry Enzyme inhibitor biology.protein Disease Progression Molecular Medicine Pharmacophore Kynurenine HeLa Cells
Zdroj:	Journal of medicinal chemistry. 52(23)
ISSN:	1520-4804
Popis:	A hydroxyamidine chemotype has been discovered as a key pharmacophore in novel inhibitors of indoleamine 2,3-dioxygenase (IDO). Optimization led to the identification of 5l, which is a potent (HeLa IC(50) = 19 nM) competitive inhibitor of IDO. Testing of 5l in mice demonstrated pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (50%) in plasma and dose dependent efficacy in mice bearing GM-CSF-secreting B16 melanoma tumors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c08716dd7a70b41a58e004af922d972 https://pubmed.ncbi.nlm.nih.gov/19507862 Zobrazit plný text záznamu