A Novel High Throughput Virtual Screening Protocol to Discover New Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors
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- Xu Haojie
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University
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- Song Yunlong
- School of Pharmacy, Second Military Medical University
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- Yang Qing
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University
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<p>Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the immune escape of tumors and has emerged as a promising target for cancer immunotherapy. Despite its potential in immuno-oncology, very few chemotypes have been reported to date. Here, we disigned a novel high throughput virtual screening (HTVS) cascade protocol, combining both pharmacophore modeling and molecular docking and it was employed to query commercially available compounds to identify novel inhibitors. Among the 23 compounds selected for the in vitro IDO1 inhibitory activity assay, five compounds exhibit greater than 20% inhibition at a test concentration of 10 µM, with two compounds having an IC50 value of 23.8 and 8.8 µM, respectively. The novel scaffold together with a ligand efficiency of 0.28 kcal/mol per heavy atom makes both compounds as suitable starting points for future chemistry elaboration. Our HTVS protocol was validated and could be employed in discovery of IDO1 inhibitors.</p>
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 65 (8), 714-717, 2017
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679153260416
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- NII論文ID
- 130005875878
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 028388402
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- PubMed
- 28768924
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
- CiNii Articles
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- 使用不可