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Discovery of small molecule degraders for modulating cell cycle

Frontiers of Medicine   Pages 823-854 doi: 10.1007/s11684-023-1027-5

Abstract: The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

Keywords： PROTAC     molecular glue     degrader     cell cycle     CDK     cyclin    

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Near-infrared benzodiazoles as small molecule environmentally-sensitive fluorophores

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 1,   Pages 128-135 doi: 10.1007/s11705-021-2080-8

Abstract: In this work, we have optimised a general and straightforward synthetic approach to prepare a small library

Keywords： fluorescence     probes     iron     screening     library    

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Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

Frontiers of Chemical Science and Engineering 2017, Volume 11, Issue 1,   Pages 15-26 doi: 10.1007/s11705-017-1629-z

Abstract: Overproduction of small-molecule chemicals using engineered microbial cells has greatly reduced the productionFor this purpose, many genetic components have been adapted into biosensors of small molecules, whichcouple the intracellular concentrations of small molecules to easily detectable readouts such as fluorescenceSuch biosensors allow a high-throughput screening of the small-molecule products, and can be roughlyThis review summarizes the recent developments in the design and applications of biosensors for small-molecule

Keywords： biosensor     small molecule product     transcription factor     riboswitch     high-throughput screening    

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Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

Xiaohuan Wang, Peng Zou, Fan Wu, Lu Lu, Shibo Jiang

Frontiers of Medicine 2017, Volume 11, Issue 4,   Pages 449-461 doi: 10.1007/s11684-017-0589-5

Abstract: In this review, we summarize and discuss the latest progress in the development of small-molecule viralWe also discuss some general strategies for developing small-molecule viral inhibitors.

Keywords： emerging and re-emerging viruses     small-molecule inhibitor     coronavirus     Ebola virus     Zika virus     life cycle    

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Recent advances of small-molecule fluorescent probes for detecting biological hydrogen sulfide

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 1,   Pages 34-63 doi: 10.1007/s11705-021-2050-1

Abstract: It was recently revealed that H2S is also an endogenous signaling molecule that has important

Keywords： hydrogen sulfide     fluorescent probe     reducibility     nucleophilicity     copper sulfide precipitate     hydrogen polysulfides    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

Frontiers of Medicine doi: 10.1007/s11684-023-1037-3

Abstract: So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivirregarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule

Keywords： COVID-19     antiviral drugs     mindeudesivir    

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A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal

Frontiers of Medicine 2023, Volume 17, Issue 2,   Pages 275-289 doi: 10.1007/s11684-022-0945-y

Abstract: The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.

Keywords： epidermal growth factor receptor     ErbB receptors     HM781-36B     nasopharyngeal carcinoma     molecular targeted therapy     cisplatin    

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Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic

Vaibhav Mundra, Ram I. Mahato

Frontiers of Chemical Science and Engineering 2014, Volume 8, Issue 4,   Pages 387-404 doi: 10.1007/s11705-014-1457-3

Abstract: There are many challenges in developing efficient and target specific delivery systems of small molecule

Keywords： nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

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Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 1,   Pages 4-33 doi: 10.1007/s11705-021-2041-2

Abstract: Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactiveSingle organic molecule fluorescent probes have been successively developed to simultaneously monitor

Keywords： bioactive molecules     fluorescent probes     in living cells and in vivo     review    

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Bright future of polymerizing small-molecule acceptors in realizing high performance all-polymer solar

Qi Chen1 , Cen Zhang1 , Lingwei Xue1,2 , Zhi-Guo Zhang1

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 10,   Pages 1526-1529 doi: 10.1007/s11705-022-2161-3

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Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-cell

Jiahui Xu, Qianqian Wang, Elaine Lai Han Leung, Ying Li, Xingxing Fan, Qibiao Wu, Xiaojun Yao, Liang Liu

Frontiers of Medicine 2020, Volume 14, Issue 1,   Pages 60-67 doi: 10.1007/s11684-019-0694-8

Abstract: Moreover, C620-0696 was cytotoxic in BPTF with a high expression of non-small-cell lung cancer (NSCLCpresents an effective strategy to target a bromodomain factor-mediated tumorigenesis in cancers with small

Keywords： BPTF     small molecule     epigenetics     non-small-cell lung cancer    

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A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets Article

Hui Xiong, Ai-Hua Zhang, Ya-Jing Guo, Xiao-Hang Zhou, Hui Sun, Le Yang, Heng Fang, Guang-Li Yan, Xi-Jun Wang

Engineering 2021, Volume 7, Issue 9,   Pages 1293-1305 doi: 10.1016/j.eng.2020.12.016

Abstract:

A herbal prescription in traditional Chinese medicine (TCM) has great complexity, with multiple components and multiple targets, making it extremely challenging to determine its bioactive compounds. Yinchenhao Tang (YCHT) has been extensively used for the treatment of jaundice disease. Although many studies have examined the efficacy and active ingredients of YCHT, there is still a lack of an in-depth systematic analysis of its effective components, mechanisms, and potential targets—especially one based on clinical patients. This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform. The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method. Moreover, a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis (IPA). We found that eight active components could modulate five key targets. These key targets were further verified by enzyme-linked immunosorbent assay (ELISA), which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase (CYP7A1), multidrug-resistance-associated protein 2 (ABCC2), multidrug-resistance-associated protein 3 (ABCC3), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and farnesoid X receptor (FXR), and by regulating metabolic pathways including primary bile acid biosynthesis, porphyrin and chlorophyll metabolism, and biliary secretion. Eight main effective compounds were discovered and correlated with the key targets and pathways. In this way, we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

Keywords： Efficacy     Bioactive compound     Small molecule     Targets     Herbal medicine     Metabolomics    

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A pseudocapacitive molecule-induced strategy to construct flexible high-performance asymmetric supercapacitors

Frontiers of Chemical Science and Engineering 2023, Volume 17, Issue 9,   Pages 1208-1220 doi: 10.1007/s11705-023-2304-1

Abstract: we present an “advantage-complementary strategy” using sodium lignosulfonate as a pseudocapacitive molecule

Keywords： molecular synergy     pseudocapacitive lignosulfonate     flexible electronic devices     asymmetric supercapacitor     wide voltage windows    

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Title Author Date Type Operation

Discovery of small molecule degraders for modulating cell cycle

Journal Article

Near-infrared benzodiazoles as small molecule environmentally-sensitive fluorophores

Journal Article

Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

Journal Article

Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

Xiaohuan Wang, Peng Zou, Fan Wu, Lu Lu, Shibo Jiang

Journal Article

Recent advances of small-molecule fluorescent probes for detecting biological hydrogen sulfide

Journal Article

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

Journal Article

A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal

Journal Article

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic

Vaibhav Mundra, Ram I. Mahato

Journal Article

Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

Journal Article

Bright future of polymerizing small-molecule acceptors in realizing high performance all-polymer solar

Qi Chen1 , Cen Zhang1 , Lingwei Xue1,2 , Zhi-Guo Zhang1

Journal Article

Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-cell

Jiahui Xu, Qianqian Wang, Elaine Lai Han Leung, Ying Li, Xingxing Fan, Qibiao Wu, Xiaojun Yao, Liang Liu

Journal Article

A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets

Hui Xiong, Ai-Hua Zhang, Ya-Jing Guo, Xiao-Hang Zhou, Hui Sun, Le Yang, Heng Fang, Guang-Li Yan, Xi-Jun Wang

Journal Article

Rao Yu: Small Molecule Targeted Protein Degradation Technology and Application (2022-12-15)

22 Dec 2022

Conference Videos

Zhong Wu: Research on Small Molecule Anti Crown Virus Drugs (2021-7-23)

23 Oct 2021

Conference Videos

A pseudocapacitive molecule-induced strategy to construct flexible high-performance asymmetric supercapacitors

Journal Article