Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

Yikai Wang; Jean Yves Wach; Patrick Sheehan; Cheng Zhong; Chenyang Zhan; Richard Harris; Steven C. Almo; Joshua Bishop; Stephen J. Haggarty; Alexander Ramek; Kayla N. Berry; Conor O'Herin; Angela N. Koehler; Alvin W. Hung; Damian W. Young

doi:10.1021/acsmedchemlett.6b00230

Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

Yikai Wang, Jean Yves Wach, Patrick Sheehan, Cheng Zhong, Chenyang Zhan, Richard Harris, Steven C. Almo, Joshua Bishop, Stephen J. Haggarty, Alexander Ramek, Kayla N. Berry, Conor O'Herin, Angela N. Koehler, Alvin W. Hung, Damian W. Young

Biochemistry

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure-activity relationship, and finally lead to the synthesis of a more potent compound.

Original language	English (US)
Pages (from-to)	852-856
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	7
Issue number	9
DOIs	https://doi.org/10.1021/acsmedchemlett.6b00230
State	Published - Sep 8 2016

Keywords

Diversity oriented synthesis
GSK3β
fragment growing
fragment-based drug discovery

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.6b00230

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Wang, Y., Wach, J. Y., Sheehan, P., Zhong, C., Zhan, C., Harris, R., Almo, S. C., Bishop, J., Haggarty, S. J., Ramek, A., Berry, K. N., O'Herin, C., Koehler, A. N., Hung, A. W., & Young, D. W. (2016). Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β. ACS Medicinal Chemistry Letters, 7(9), 852-856. https://doi.org/10.1021/acsmedchemlett.6b00230

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AU - Wang, Yikai

AU - Wach, Jean Yves

AU - Sheehan, Patrick

AU - Zhong, Cheng

AU - Zhan, Chenyang

AU - Harris, Richard

AU - Almo, Steven C.

AU - Bishop, Joshua

AU - Haggarty, Stephen J.

AU - Ramek, Alexander

AU - Berry, Kayla N.

AU - O'Herin, Conor

AU - Koehler, Angela N.

AU - Hung, Alvin W.

AU - Young, Damian W.

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AB - Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure-activity relationship, and finally lead to the synthesis of a more potent compound.

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KW - fragment growing

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Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

Abstract

Keywords

ASJC Scopus subject areas

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