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10.3389/fphar.2018.00277

http://scihub22266oqcxt.onion/10.3389/fphar.2018.00277
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suck abstract from ncbi


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pmid29651242
      Front+Pharmacol 2018 ; 9 (ä): 277
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  • Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening #MMPMID29651242
  • Zhang G ; Xing J ; Wang Y ; Wang L ; Ye Y ; Lu D ; Zhao J ; Luo X ; Zheng M ; Yan S
  • Front Pharmacol 2018[]; 9 (ä): 277 PMID29651242 show ga
  • Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC(50) of 21.61 ?M on enzymatic level and 89.11 ?M on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC(50) about 18 ?M on both enzymatic level and cellular level. The structure-activity relationship (SAR) of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development.
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