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Yuting Gao

Bio: Yuting Gao is an academic researcher from Chongqing University. The author has an hindex of 1, co-authored 1 publications receiving 1 citations.

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Journal ArticleDOI
Gong Zhang1, Juan Zhang1, Yuting Gao1, Yangfeng Li1, Yizhou Li1 
TL;DR: The concept of undruggable targets was introduced in this article, which refers to clinically meaningful therapeutic targets that are "difficult to drug" or "yet to be drugged" via traditional approaches.
Abstract: Introduction Undruggable targets refer to clinically meaningful therapeutic targets that are 'difficult to drug' or 'yet to be drugged' via traditional approaches. Featuring characteristics of lacking defined ligand-binding pockets, non-catalytic protein-protein interaction functional modes and less-investigated 3D structures, these undruggable targets have been targeted with novel therapeutic entities developed with the progress of unconventional drug discovery approaches, such as targeted degradation molecules and display technologies. Area covered This review first presents the concept of 'undruggable' exemplified by RAS and other targets. Next, detailed strategies are illustrated in two aspects: innovation of therapeutic entities and development of unconventional drug discovery technologies. Finally, case studies covering typical undruggable targets (Bcl-2, p53, and RAS) are depicted to further demonstrate the feasibility of the strategies and entities above. Expert opinion Targeting the undruggable expands the scope of therapeutically reachable targets. Consequently, it represents the drug discovery frontier. Biomedical studies are capable of dissecting disease mechanisms, thus broadening the list of undruggable targets. Encouraged by the recent approval of the KRAS inhibitor Sotorasib, we believe that merging multiple discovery approaches and exploiting various novel therapeutic entities would pave the way for dealing with more 'undruggable' targets in the future.

19 citations


Cited by
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TL;DR: The high conversion and wide substrate-scope property of the protocol render its feasibility in the manipulation of terminal amines on oligonucleotide conjugates, including "cap-and-catch" purification, sequential synthesis during DEL construction, and on-DNA macrocyclization.
Abstract: The incorporation of the isoindole core into the DNA-encoded chemical library is highly desirable for the great potential pharmacological characters exampled by molecules like lenalidomide. Herein, we reported a DNA-compatible protocol for the OPA-mediated transformation of amines into drug-like moieties represented by isoindolinone and thio-2-isoindole, respectively. The high conversion and wide substrate-scope property of our protocol render its feasibility in the manipulation of terminal amines on oligonucleotide conjugates, including "cap-and-catch" purification, sequential synthesis during DEL construction, and on-DNA macrocyclization.

17 citations

Journal ArticleDOI
TL;DR: A visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes is presented, demonstrating the feasibility of this approach in DNA-encoded chemical library construction.

14 citations

Journal ArticleDOI
Juan Zhang1, Xianfeng Li1, Haimei Wei1, Yangfeng Li1, Gong Zhang1, Yizhou Li1 
TL;DR: A sequential DNA-encoded synthesis strategy for polysubstituted pyrazoline heterocycles, which fuses a broad panel of aldehydes, aryl amines, and alkenes as building blocks, was presented in this paper.

11 citations

Journal ArticleDOI
TL;DR: Highly efficient bond linkages of C-C, C-N, and C-S were achieved to fuse building blocks that are widely commercially available and DNA-encoding compatibility of the method has been further demonstrated.

9 citations

Journal ArticleDOI
TL;DR: In this article , the authors proposed a large encoding design (LED) for DNA-encoded chemical libraries, which facilitates the PCR-amplification of multiple codes distributed among two partially complementary DNA strands.
Abstract: DNA-encoded chemical libraries (DELs) are useful tools for the discovery of small molecule ligands to protein targets of pharmaceutical interest. Compared with single-pharmacophore DELs, dual-pharmacophore DELs simultaneously display two chemical moieties on both DNA strands, and allow for the construction of highly diverse and pure libraries, with a potential for targeting larger protein surfaces. Although methods for the encoding of simple, fragment-like dual-display libraries have been established, more complex libraries require a different encoding strategy. Here, we present a robust and convenient “large encoding design” (LED), which facilitates the PCR-amplification of multiple codes distributed among two partially complementary DNA strands. We experimentally implemented multiple coding regions and we compared the new DNA encoding scheme with previously reported dual-display DEL modalities in terms of amplifiability and performance in test selections against two target proteins. With the LED methodology in place, we foresee the construction and screening of DELs of unprecedented sizes and designs.

7 citations