國家衛生研究院 NHRI:Item 3990099045/13875

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shau-Hua Ueng > Periodical Articles > Item 3990099045/13875

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13875

Title:	Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl)amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design
Authors:	Yeh, TK;Song, JS;Chang, PW;Yu, JC;Chang, CH;Liao, FY;Tien, YW;Kuppusamy, R;Li, AS;Chen, CH;Chen, CW;Lin, LM;Chang, HH;Huang, CH;Yao, JY;Wu, MH;Peng, YH;Hsueh, CC;Hsiao, WC;Chen, PH;Lin, CY;Hsieh, SH;Shih, C;Hung, MS;Wu, SY;Kuo, CC;Ueng, SH
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Indoleamine 2,3-dioxygenase-1 (IDO1) is a potential target for the next generation of cancer immunotherapies. We describe the development of two series of IDO1 inhibitors incorporating a N-hydroxy-thiophene-carboximidamide core generated by knowledge-based drug design. Structural modifications to improve the cellular activity and pharmacokinetic (PK) properties of the compounds synthesized, including extension of the side chain of the N-hydroxythiophene-2-carboximidamide core, resulted in compound 27a, a potent IDO1 inhibitor which demonstrated significant (51%) in vivo target inhibition on IDO1 in a human SK-OV-3 ovarian xenograft tumor mouse model. This strategy is expected to be applicable to the discovery of additional IDO1 inhibitors for the treatment of other diseases susceptible to modulation of IDO1.
Date:	2022-02-05
Relation:	European Journal of Medicinal Chemistry. 2022 Feb 5;229:Article number 114043.
Link to:	http://dx.doi.org/10.1016/j.ejmech.2021.114043
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000766121600003
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85121273827
Appears in Collections:	[Shau-Hua Ueng] Periodical Articles [Ching-Chuan Kuo] Periodical Articles [Su-Ying Wu] Periodical Articles [Ming-Shiu Hung] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Teng-Kuang Yeh] Periodical Articles

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