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Inhibiting cancer cell hallmark features through nuclear export inhibition

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Signal Transduction and Targeted Therapy 2016年第1期1卷 91-100页

作者： Qingxiang Sun Xueqin Chen Qiao Zhou Ezra Burstein shengyong yang Da Jia State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy Sichuan UniversityChengduChina Department of Pathology West China HospitalSichuan UniversityChengduChina Department of Internal Medicine UT Southwestern Medical CenterDallasTexasUSA Department of Molecular Biology UT Southwestern Medical CenterDallasTexasUSA West China 2nd University Hospital Sichuan UniversityChengduChina

Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical *** export factor chromosomal region maintenance 1(CRM1;Xpo1 and exportin-1)controls cellular localization and function of numerous proteins that are critical for the development of many cancer *** diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials(phase I–III)on both advanced-stage solid and hematological *** this review,we compare and contrast the mechanisms of action of different CRM1 inhibitors,and discuss the potential benefit of unexplored non-covalent CRM1 *** emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

关键词： attractive likely benefit

Antimicrobial peptide DP7 with potential activity against SARS coronavirus infections

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1420-1422页

作者： Rui Zhang Xiaohua Jiang Jingxin Qiao Zeng Wang Aiping Tong Jinliang yang shengyong yang Li yang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduChina

Dear Editor,The outbreak of the SARS-CoV-2 epidemic once again demonstrates that RNA viruses,through mutations,genetic recombination and cross-species transmission,can pose a serious threat to the health of people *** after the severe acute respiratory syndrome(SARS)and middle east respiratory syndrome(MERS)outbreaks,the world still initially lacked effective means to control the current coronavirus disease 2019(COVID-19)*** must work together to develop effective drugs to treat existing and future potential coronavirus infections to reduce their impact on the global health system and human *** to time constraints,the'conventional drug in new use#method has become the main method of treating SARS-CoV-2 ***,long-term drug development goals should include treatments that can produce broad-spectrum effects on different coronaviruses,and provide the means to alleviate disease symptoms and prevent death.

关键词： infections drugs SARS

Interpretation on Discipline Value of Political Scientist Elinor's Academic Achievements

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学术界 2010年第12期 249-250页

作者： Chen shengyong yang Fengyin College of Public Administration,Zhejiang University

As a political scientist,Elinor Ostrom won 2009 Nobel Prize in economics,which caused great repercussions in the academic circles of politics and *** paper,based on the backward and weak situation that modern political science faced in the pursuit of scientific process gives an interpretation on discipline value of Elinor Ostrom’s academic achievements from three dimensions,which consist of scientific status,functions and *** it also reveals that the combination of theoretical research and empirical research,interdisciplinary research methods,specific academic research inclination,multiple academic cooperation and exchange not only contributed to Elinor’s success but also reflected the main development trend of political science.

关键词： Politics Discipline Discipline Integration

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials

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Signal Transduction and Targeted Therapy 2019年第1期4卷 63-101页

作者： Yuan Cheng Cai He Manni Wang Xuelei Ma Fei Mo shengyong yang Junhong Han Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina

Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying *** dysregulation is often linked to human disease,notably *** the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical *** this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

关键词： epigenetic clinical drugs

Recent advances in small-molecular therapeutics for COVID-19

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Precision Clinical Medicine 2022年第4期5卷 222-243页

作者： Lei Zhong Zhipeng Zhao Xuerun Peng Jun Zou shengyong yang Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China Center for Clinical Translational Innovations Molecular Medicine Research CenterWest China Biomedical Big Data CenterState Key Laboratory of BiotherapyWest China HospitalWest China School of MedicineSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China School of MedicineSichuan UniversityChengdu 610041China

The COVID-19 pandemic poses a fundamental challenge to global *** the outbreak of SARS-CoV-2,great efforts have been made to identify antiviral strategies and develop therapeutic drugs to combat the *** are different strategies for developing small molecular anti-SARS-CoV-2 drugs,including targeting coronavirus structural proteins(*** protein),non-structural proteins(nsp)(***,Mpro,PLpro,helicase,nsp14,and nsp16),host proteases(***2,cathepsin,and furin)and the pivotal proteins mediating endocytosis(***),as well as developing endosome acidification agents and immune response *** and chloroquine are the anti-SARS-CoV-2 agents that were identified earlier in this epidemic and repurposed for COVID-19 clinical therapy based on these ***,their efficacies are ***,three small molecular anti-SARSCoV-2 agents,remdesivir,molnupiravir,and Paxlovid(PF-07321332 plus ritonavir),have been granted emergency use authorization or approved for COVID-19 therapy in many countries due to their significant curative effects in phase Ⅲ ***,a large number of promising anti-SARS-CoV-2 drug candidates have entered clinical *** development of these drugs brings hope for us to finally conquer *** this account,we conducted a comprehensive review of the recent advances in small molecule anti-SARS-CoV-2 agents according to the target *** we present all the approved drugs and most of the important drug candidates for each target,and discuss the challenges and perspectives for the future research and development of anti-SARS-CoV-2 drugs.

关键词： COVID-19 SARS-CoV-2 RdRp inhibitor Mpro inhibitor host-targeted inhibitor small molecule

Small molecules in targeted cancer therapy:advances,challenges,and future perspectives

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1732-1779页

作者： Lei Zhong Yueshan Li Liang Xiong Wenjing Wang Ming Wu Ting Yuan Wei yang Chenyu Tian Zhuang Miao Tianqi Wang shengyong yang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengduSichuanPeople's Republic of China Personalized Drug Therapy Key Laboratory of Sichuan Province Department of PharmacySichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuanPeople’s Republic of China

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs,targeted therapeutic drugs have become mainstream cancer *** the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration(FDA)in 2001,an increasing number of small-molecule targeted drugs have been developed for the treatment of *** December 2020,89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration(NMPA)of *** great progress,small-molecule targeted anti-cancer drugs still face many challenges,such as a low response rate and drug *** better promote the development of targeted anti-cancer drugs,we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target *** present all the approved drugs as well as important drug candidates in clinical trials for each target,discuss the current challenges,and provide insights and perspectives for the research and development of anti-cancer drugs.

关键词： drugs chemotherapy treatment

Crystal structure of SARS-CoV-2 nsp10/nsp162′-O-methylase and its implication on antiviral drug design

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1251-1254页

作者： Sheng Lin Hua Chen Fei Ye Zimin Chen Fanli yang Yue Zheng Yu Cao Jingxin Qiao shengyong yang Guangwen Lu West China Hospital Emergency Department(WCHED) State Key Laboratory of Biotherapy and Cancer CenterWest China Hospital and Collaborative Innovation Center of BiotherapySichuan University610041 ChengduSichuanChina Disaster Medicine Center West China HospitalSichuan University610041 ChengduSichuanChina

Dear Editor,The unexpected outbreak of a novel human coronavirus infection has imposed great threat to public *** far,this newly-identified virus has spread to 215 countries and territories,infected more than 3.5 million people,and caused over 240,000 deaths worldwide.1 Although intensified countermeasures have been implemented globally to control the virus infection,the pandemic is still surging with a daily increase in infection case of over 65,000 ever since April 1st 2020.1 No prophylactic vaccines or clinical drugs are currently available to prevent or treat the disease,namely coronavirus disease 2019(COVID-19).

关键词： infection drugs intensified

Deciphering the regulatory and catalytic mechanisms of an unusual SAM-dependent enzyme

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Signal Transduction and Targeted Therapy 2019年第1期4卷 530-537页

作者： Qiu Sun Yuehong Hu Yijun Gu Jiangkun Huang Jun He Lan Luo Yi yang Shuo Yin Chao Dou Tianqi Wang Xianghui Fu Ling He Shiqian Qi Xiaofeng Zhu shengyong yang Xiawei Wei Wei Cheng Division of Respiratory and Critical Care Medicine Center of Infectious DiseasesNational Clinical Research Center for Geriatrics and State Key Laboratory of BiotherapyWest China Hospital of Sichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Shanghai Synchrotron Radiation Facility Zhangjiang LabZhangheng Road 239Pudong DistrictShanghai 201203China Department of Medicinal Chemistry Key Laboratory of Drug-Targeting and Drug Delivery System of the Education MinistrySichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China West China School of Public Health Sichuan UniversityChengdu 610041China

S-adenosyl-1-methionine(SAM)-dependent enzymes regulate various disease-related behaviors in all ***,the leporin biosynthesis enzyme LepI,a SAM-dependent enzyme,was reported to catalyze pericyclic reactions in leporin biosynthesis;however,the mechanisms underlying LepI activation and catalysis remain *** study aimed to investigate the molecular mechanisms of ***,we reported crystal structures of LepI bound to SAM/5′-deoxy-5′-(methylthio)adenosine(MTA),S-adenosyl-homocysteine(SAH),and SAM/substrate *** and biochemical analysis revealed that MTA or SAH inhibited the enzyme activities,whereas SAM activated the *** analysis of the substrate-bound structure of LepI demonstrated that this enzymatic retro-Claisen rearrangement was primarily driven by three critical polar residues His133,Arg197,Arg295 around the active site and assisted by SAM with unclear *** present studies indicate that the unique mechanisms underlying regulatory and catalysis of the unusual SAM-dependent enzyme LepI,not only strengthening current understanding of the fundamentally biochemical catalysis,but also providing novel insights into the design of SAM-dependent enzyme-specific small molecules.

关键词： mechanism. catalysis unusual

Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm

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Journal of Molecular Cell Biology 2017年第4期9卷 262-273页

作者： Bo Chen Jiawen Teng Hongwei Liu Xu Pan Ya Zhou Shu Huang Mowen Lai Guohui Bian Bin Mao Wencui Sun Qiongxiu Zhou shengyong yang Tatsutoshi Nakahata Feng Ma Institute of Blood Transfusion Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) Chengdu 610052 China State Key Laboratory of Biotherapy Sichuan University Chengdu 610065 China Center for iPS Cell Research and Application (CiRA) Kyoto University Kyoto 606-8507 Japan State Key Laboratory of Experimental Hematology CAMS & PUMC Tianjin 300020 China

RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.

关键词： RUNX1/AML1 hematopoiesis hemogenic endothelium mesoderm TGF-β signaling pathway hESC inducible expressionsystem