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Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

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Acta Pharmaceutica Sinica B 2022年第2期12卷 532-557页

作者： Leilei Fu Wenke Jin Jiahui Zhang Lingjuan Zhu Jia Lu Yongqi Zhen Lan Zhang Liang Ouyang Bo Liu Haiyang Yu Sichuan Engineering Research Center for Biomimetic Synthesis of Natural drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State key laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China College of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110064China State key laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved *** non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy,with potentially lower overall costs and shorter *** non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers,with the aid of some new emerging technologies,such as omics sequencing and artificial intelligence to overcome the bottleneck of drug ***,in this review,we focus on summarizing the therapeutic potential of non-oncology drugs,including cardiovascular drugs,microbiological drugs,small-molecule antibiotics,anti-viral drugs,anti-inflammatory drugs,antineurodegenerative drugs,antipsychotic drugs,antidepressants,and other drugs in human *** also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer *** together,these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

关键词： drug repurposing Non-oncology drug Cancer therapy Cardiovascular drug Microbiological drug Small-molecule antibiotics Anti-viral drug Anti-inflammatory drug

gem-Dimethyl-bearing C-Glucosides as Sodium-glucose Co-transporter 2 （SGLT2） Inhibitors

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Chinese Journal of Chemistry 2011年第6期29卷 1192-1198页

作者： Shi, Yongheng Zhao, Guilong Lou, Yuanyuan Wang, Yuli Shao, Hua Liu, Wei Xu, Weiren Tang, Lida School of Pharmacy Tianjin Medical University Tianjin 300070 China tianjin key laboratory of Molecular Design and drug Discovery Tianjin Institute of Pharmaceutical Research Tianjin 300193 China College of Chemistry and Molecular Engineering Qingdao University of Science and Technology Qingdao Shandong 266042 China

Three novel gem-dimethyl C-glucosides were designed as sodium-glucose co-transporter 2 （SGLT2） inhibitors, and their syntheses started from D-glucose and three 2-substituted-5-bromobenzoic acids were achieved via a facile 8-step protocol, with the key step being anhydrous aluminum chloride-catalyzed Friedel-Crafts alkylation of tertiary alcohols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral glucose tolerance test （OGTT）, and the anti-hyperglycemic activities of all these three compounds were comparable with that of the positive control Dapagliflozin.

关键词： sodium-glucose co-transporter 2 (SGLT2) gem-dimethyl synthesis Friedel-Crafts alkylation oral glucose tolerance test (OGTT)

How does the addition of mushrooms and their dietary fibre affect starchy foods

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Journal of Future Foods 2022年第1期2卷 18-24页

作者： Hui Zhao Liwen Wang Margaret Brennan Charles Brennan tianjin key laboratory of Food and Biotechnology Tianjin International Joint Center of Food Science and EngineeringState Experimental and Training Centre of Food and DrugSchool of Biotechnology and Food ScienceTianjin University of CommerceTianjin 300134China College of Food Science and Technology Hebei Agricultural UniversityBaoding 071001China Department of Wine Food and Molecular BiosciencesLincoln UniversityChristchurch 7647New Zealand School of Science RMIT UniversityMelbourne3000Australia

Mushrooms contain multiple bioactive compounds of which dietary fibre is a representative *** of extracted or naturally derived dietary fibre in staple starchy foods constitutes a strategy to increase fibre intake in terms of cardiovascular disease and other metabolic *** matrix is viewed as a physical domain containing nutrients in which interactions and behaviours are different from those in isolation or free *** nutritional effect of mushrooms'addition in the starchy food matrix is reviewed together with the alterations of cooking *** studies include nutrients bioaccessibility due to the interfere of dietary fibres in consideration of their types and *** future approach to shaping microbial colonisation in the digestive tract through metabolites such as short-chain fatty acids from dietary fibres is required to sustain host physiology and health.

关键词： Food matrix Dietary fibre Mushroom Starchy foods Bioavailability

Influence of Hydrogen Bonding on the Temperature-Accelerated Hydrolysis of Silicone Based Polyetherurethane

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Chinese Journal of Polymer Science 2023年第8期41卷 1230-1237,I0007页

作者： He-Cheng Wu Shu-Ren Shao Shuo-Hong Dong Ao Wang Zhen Li Xiang-Long Han Feng Luo Jie-Hua Li Dai-Guo Zhao Wan-Ling Lan Hong Tan College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringMed-X Center for MaterialsSichuan UniversityChengdu 610065China State key laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Institute for Food and drug Control Chengdu 611731China

Temperature-accelerated in vitro degradation was established to estimate the longevity of polyurethane applied for long-term ***,the prediction did not correlate well with the data from clinical explants and the rationality of accelerated in vitro test is still in a controversial due to the *** improve the accuracy of the in vitro prediction,the influence of hydrogen bonding(HB)on the accelerated hydrolysis of silicone based polyetherurethans(SPEUs)extended with three side *** the temperature-controlled FTIR and the physical properties after temperature-accelerated in vitro degradation,it was demonstrated that side chain could increase the degree of hydrogen bond dissociation at higher temperature,resulting in the decrease of the calculated activation energy(E_(a))of *** low temperatures,changes in surface morphology and molar mass of PEUs are minimal and HB are less easily dissociated,which had barely impact on the hydrolysis *** was proposed that the E_(a) will not be impacted and that the accuracy of prediction will be increased if the acceleration temperature is lower than 70℃ and HB change is less than 15%.

关键词： Polyether urethane Polydimethylsiloxane Activation energy Hydrogen bonding Hydrolysis resistance

Chemokine-like factor 1 (CKLF1) is expressed in myocardial ischemia injury in vivo and in vitro

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BIOCELL 2024年第6期48卷 981-990页

作者： JULING FENG HAODONG CHEN YANGBO LIU QIDI AI YANTAO YANG LEI ZHAO SHIFENG CHU NAIHONG CHEN School of Pharmacy Department of PharmacyHunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction PiecesHunan University of Chinese MedicineChangsha410208China Department of Pharmacology State Key Laboratory of Bioactive Substances and Functions of Natural MedicinesInstitute of Materia Medica&Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Department of Diagnostics Research Lab of Translational Medicine Hengyang Medical CollegeUniversity of South ChinaHengyang421001China Department of Gastrointestinal Surgery The First Affiliated HospitalHengyang Medical CollegeUniversity of South ChinaHengyang421001China

Introduction:Chemokine-like factor 1(CKLF1)is a chemokine that is overexpressed in several *** previousﬁndings revealed a signiﬁcant increase in CKLF1 expression in the ischemic brain,suggesting its potential as a therapeutic target for ischemic ***:In this study,we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac *** infarction(MI)was induced in vivo by ligation of the left anterior descending artery(LAD)of the rat *** levels of CKLF1,Creatine Kinase MB Isoenzyme(CK-MB),and Lactate dehydrogenase(LDH)in the serum were detected using Enzyme-linked immunosorbent assay(ELISA).The expression of CKLF1 in the infarcted area was detected by immunohistochemistry,immunoﬂuorescence,quantitative PCR(qPCR),and Western blotting(WB).H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation(OGD).LDH was used to detect cell damage,and CKLF1 expression was detected by qPCR and ***:CKLF1 mRNA and protein expression were signiﬁcantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after *** serum CK-MB in rats increased signiﬁcantly on theﬁrst day after infarction,while the LDH concentration increased signiﬁcantly on the third day after ***1 blood levels signiﬁcantly increased on theﬁrst day following MI in ***1 expression notably increased in the infarct area on days 1,3,and 7 *** MI tissue,CKLF1 colocalizes with cardiomyocytes,macrophages,and ***:CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils,indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction.

关键词： Chemokine-like factor 1 Overexpression Myocardial infarction

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4949-4963页

作者： Pengju Yan Ningning Li Ming Ma Zhaoli Liu Huicui Yang Jinnan Li Chunlei Wan Shuliu Gao Shuai Li Longtai Zheng John LWaddington Lin Xu Xuechu Zhen Jiangsu key laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China CAS key laboratory of Animal Models and Human Disease Mechanisms and KIz-sU Joint Laboratory of Animal Model and Drug Developmentand Laboratory of Learning and MemoryKunming Institute of Zoologythe Chinese Academy of SciencesKunming 650223China School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin 2Ireland

Substance use disorder remains a major challenge,with an enduring need to identify and evaluate new,translational targets for effective ***,we report the upregulation of Hypoxia-inducible factor-1α(HIF-1α)expression by roxadustat(Rox),a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α,administered either systemically or locally into selected brain regions,suppressed morphine(Mor)-induced conditioned place preference(CPP).

关键词： drug morphine anemia

high-gravity technology intensified Knoevenagel condensation-Michael addition polymerization of poly (ethylene glycol)-poly (n-butyl cyanoacrylate) for blood-brain barrier delivery

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Chinese Journal of Chemical Engineering 2022年第6期35卷 94-103页

作者： Xingzheng Liu Chuanbo Fu Manting Wang Jiexin Wang Haikui Zou Yuan Le Jianfeng Chen State key laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China Research Centre of the Ministry of Education for high Gravity Engineering and Technology Beijing University of Chemical TechnologyBeijing 100029China

Poly(ethylene glycol)-poly(n-butyl cyanoacrylate)(PEG-PBCA)is a remarkable drug delivery carrier for permeating blood-brain *** this work,a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA.A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than ***,the reaction time reduced 60%compared to conventional stirred tank reactor *** structures of as-prepared polymers were *** vitro drug delivery performance was *** cytotoxicity of PEG-PBCA to brain microvessel endothelial cells(BMVEC)decreases with the extension of the PEG chain and the shortening of the PBCA *** polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG *** of bloodbrain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation,while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride(Dox).The average apparent permeability coeffi-cient increased 1.7 and 0.25 times than that of raw Nile red and Dox,***-gravity intensi-fied condensation polymerization should have great potential in brain drug delivery system.

关键词： high-gravity technology Knoevenagel condensation-Michael addition polymerization Poly(ethylene glycol)-poly(n-butyl cyanoacrylate) Blood-brain barrier Polymerization Reactors

Recent advances in nanomedicines for the treatment of ischemic stroke

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1767-1788页

作者： Chao Li Tao Sun Chen Jiang key laboratory of Smart drug delivery Ministry of EducationState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceDepartment of PharmaceuticsSchool of PharmacyResearch Center on Aging and MedicineFudan UniversityShanghai 201203China

Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the *** would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain,where the ischemic cascade eventually leads to cell death and brain *** researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic ***,traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment *** provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo,achieve effective drug accumulation at the target site,enhance the therapeutic effect and meanwhile reduce the side *** this review,we comprehensively describe the pathophysiology of stroke,traditional treatment strategies and emerging nanomedicines,summarize the barriers and methods for transporting nanomedicine to the lesions,and illustrate the latest progress of nanomedicine in treating ischemic stroke,with a view to providing a new feasible path for the treatment of cerebral ischemia.

关键词： Stroke Ischemic cascade Reperfusion Neuroprotectant Thrombolytics Nanomedicine Blood-brain barrier

Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication

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Acta Pharmaceutica Sinica B 2015年第6期5卷 577-582页

作者： Jiaying Han Yinjing Sun Jiapeng Hou Yuyan Wang Yu Liu Cao Xie Weiyue Lu Jun Pan Department of Pharmaceutics School of PharmacyFudan University key laboratory of Smart drug delivery (Fudan University) Ministry of Education Department of Microbiology Shanghai Medical CollegeFudan University

This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles(SMINs) designed to adhere to Helicobacter pylori(***).Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method.A fraction of Lpp20,an outer membrane protein of *** known as NQA,was chosen as template and modified with myristic acid to facilitate its localization on the surface of the *** interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance(SPR),change in zeta potential and fluorescence polarization(FP).The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control *** vitro experiments also indicate that such SMINs are able to adhere to *** and may be useful for *** eradication.

关键词： Surface molecularly imprinted nanoparticles Epitope imprinting NQA Lpp20 Helicobacter pylori binding