Author
Wenyin Shen
Bio: Wenyin Shen is an academic researcher from University of Hong Kong. The author has contributed to research in topics: Chemical library & Drug discovery. The author has an hindex of 1, co-authored 3 publications receiving 17 citations.
Papers
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TL;DR: An anchor-directed DEDL approach is reported that can identify full ligand structures from large-scale D EDLs and is able to convert unbiased libraries to focused ones targeting specific protein classes.
Abstract: Dynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA-encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. We report an anchor-directed DEDL approach that can identify full ligand structures from large-scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. We demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti-cancer drug target. This work may provide a broadly applicable method for inhibitor discovery.
36 citations
TL;DR: This study replaced p-stilbazole with psoralen (PS) and tested the feasibility of Psoralen as the crosslinker in DEDL selection to greatly facilitate the development of DEDls as a versatile tool in drug discovery.
10 citations
TL;DR: In this article, a 10,000-member DNA-encoded dynamic combinatorial library (DCL) was selected against sirtuin-1, 2, and 5 domains of bromodomain 4 (BRD4), respectively.
1 citations
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TL;DR: Synthetic application in both the derivatization of obtained diene products and the on-DNA synthesis of DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.
Abstract: Using gem-difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes are well-tuned by Rh/Ir-catalyzed system; in the RhIII catalysis, 3-alkenyl-1H-isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons are afforded in a solvent-dependent manner whereas difluoromethylene-substituted 1H-isochromen-1-ones are generated under the IrIII -catalyzed system. Mechanistic studies revealed that unusually double β-F eliminations and fluorine effect-induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on-DNA synthesis of DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.
46 citations
TL;DR: The recent progress in using DNA-encoded chemical libraries to interrogate complex biological targets and their potential to identify structures that elicit function or possess other useful properties are discussed.
31 citations
01 Oct 2020
TL;DR: While this single‐molecule approach can provide viable information on the effects of ligand arrangements on bidentate protein binding, in‐depth investigations into the nature of local microenvironments will be required to exploit its full potential.
29 citations
TL;DR: High-power screening (HPS) as discussed by the authors has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.
24 citations
TL;DR: High-power screening (HPS) as mentioned in this paper has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.
24 citations