title: Establishment of a human indoleamine 2, 3-dioxygenase 2 (hIDO2) bioassay system and discovery of tryptanthrin derivatives as potent hIDO2 inhibitors.
abstract: As an analogue of IDO1 (indoleamine 2, 3-dioxygenase 1), the well-known new therapeutic target, IDO2 is receiving increased attention. Herein, the expression and purification of recombinant human IDO2 (hIDO2) and the establishment of a hIDO2 bioassay system on both enzymatic and cellular levels are described. Nine tryptanthrin derivatives were screened for potential hIDO2 inhibitory activities, and their Ki values, enzymatic and cellular IC50 values, as well as the types of inhibition were measured. The typtanthrin derivatives 5i, 5c and 5d (especially 5i) were found to be potent hIDO2 inhibitors with superior efficiency far better than that of the most frequently-used inhibitor L-1-MT. Two ultimate purposes of the present study have been achieved: establishing an IDO2 bioassay system and screening novel IDO2 inhibitors that can be used (directly or with some modifications) for potential therapeutic applications.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
authors.forename: Zhanling
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Chemistry, Tongji University, Siping Road 1239, Shanghai, 200092, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Kuang
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China; Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. Electronic address: yangqing68@fudan.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
mesh_terms: D004796:Clinical Enzyme Tests; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; C576711:IDO2 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011799:Quinazolines; D011994:Recombinant Proteins; C046243:tryptanthrine
keywords: 3-dioxygenase 2; IDO2 bioassay system; IDO2 inhibitor; Indoleamine 2; Tryptanthrin derivatives