Discovery of Potent Competitive Inhibitors of Indoleamine 2,3-Dioxygenase with in Vivo Pharmacodynamic Activity and Efficacy in a Mouse Melanoma Model

作者：Yue Eddy W; Douty Brent; Wayland Brian; Bower Michael; Liu Xiangdong; Leffet Lynn; Wang Qian; Bowman Kevin J; Han**ury Michael J; Liu Changnian; Wei Min; Li Yanlong; Wynn Richard; Burn Timothy C; Koblish Holly K; Fridman Jordan S; Metcalf Brian; Scherle Peggy A; Combs Andrew P^*

来源：Journal of Medicinal Chemistry, 2009, 52(23): 7364-7367.

DOI：10.1021/jm900518f

A hydroxyamidine chemotype has been discovered as a key pharmacophore in novel inhibitors of indoleamine 2,3-dioxygenase (I DO). 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 I DO, as measured by decreased kynurenine levels (> 50%) in plasma and dose dependent efficacy in mice hearing GM-CSF-secreting B16 melanoma tumors.

• 出版日期2009-12-10