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Discovery, Optimization, and Evaluation of Potent and Highly Selective PI3Kγ-PI3Kδ Dual Inhibitors. 2019
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
Hutchison MediPharma Limited , Building 4, 720 Cai Lun Road, Zhangjiang Hi-Tech Park , Shanghai 201203 , China.
An electronic density model was developed and used to identify a novel pyrrolotriazinone replacement for a quinazolinone, a commonly used moiety to impart selectivity in inhibitors for PI3Kγ and PI3Kδ. Guided by molecular docking, this new specificity piece was then linked to the hinge-binding region of the inhibitor using a novel cyclic moiety. Further structure-activity relationship optimization around the hinge region led to the discovery of candidate 26, a highly potent and selective PI3Kγ-PI3Kδ dual inhibitor with favorable drug metabolism and pharmacokinetic properties in preclinical species.
Related Publications
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
October 2020,
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Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
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Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
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Jennifer Venable, and
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Scott D Bembenek
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Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
January 2020,
Bioorganic & medicinal chemistry letters,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
July 2017,
Bioorganic & medicinal chemistry letters,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
February 2017,
Bioorganic & medicinal chemistry letters,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
November 2020,
ACS medicinal chemistry letters,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
September 2023,
Bioorganic chemistry,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
May 2018,
European journal of medicinal chemistry,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
January 2016,
Journal of medicinal chemistry,
Hong Jia, and
Guangxiu Dai, and
Weiguo Su, and
Kun Xiao, and
Jianyang Weng, and
Zhulin Zhang, and
Qing Wang, and
Tianhai Yuan, and
Fuying Shi, and
Zheng Zhang, and
Wei Chen, and
Yang Sai, and
Jian Wang, and
Xiong Li, and
Yu Cai, and
Jun Yu, and
Ping Ren, and
Jennifer Venable, and
Tadimeti Rao, and
James P Edwards, and
Scott D Bembenek
January 2021,
ACS medicinal chemistry letters,
