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Development of small molecule drugs targeting immune checkpoints 被引量:1
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作者 Luoyi Chen Xinchen Zhao +3 位作者 Xiaowei Liu Yujie Ouyang Chuan Xu Ying Shi 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第5期382-399,共18页
Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune chec... Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration. 展开更多
关键词 Immune checkpoints small molecule drugs programmed death protein 1 CD47 signal-regulatory proteinα
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Unmodified methodologies in target discovery for small molecule drugs:A rising star 被引量:1
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作者 Jiayue Tang Meng Ou +1 位作者 Qiuling Zheng Ya Ding 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第12期4980-4988,共9页
Target discovery,involving target identification and validation,is the prerequisite for drug discovery and screening.Novel methodologies and technologies for the precise discovery and confirmation of drug targets are ... Target discovery,involving target identification and validation,is the prerequisite for drug discovery and screening.Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease,looking for a drug and elucidating the mechanism of drug treatment.Among the common target identification and confirmation methods,the modified method is time-consuming and laborious,which may reduce or change the activity of natural products.The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets.A wide range of unmodified approaches have been reported,introducing and analyzing the recent emerging methodologies and technologies.This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs.The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research. 展开更多
关键词 Target discovery Target identification small molecule drug METHODOLOGIES Unmodified
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Expert Consensus on the Clinical Application of Oral Small-molecule Antiviral Drugs Against COVID-19
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作者 Nanshan Zhong Guiqiang Wang 《Infectious Diseases & Immunity》 CSCD 2024年第4期158-169,共12页
Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for n... Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China.Although a variety of small‑molecule antiviral drugs against COVID‑19 have been listed in China,there is no specific drug recommendation for special populations.Society of Bacterial Infection and Resistance of Chinese Medical Association,together with the National Clinical Research Center for Respiratory Disease,and the National Center for Respiratory Medicine,organized domestic experts in various fields such as respiratory,virology,infection,critical care,emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small‑Molecule Antiviral Drugs against COVID‑19.The main content of this consensus includes the introduction of seven small‑molecule antiviral drugs against COVID‑19,focusing on the drug recommendations for 14 special groups such as the elderly,patients with complicated chronic diseases,tumor patients,pregnant women,and children,and providing suggestions for clinicians to standardize drug use. 展开更多
关键词 Coronavirus infections Antiviral therapy small molecule drugs Early stage Expert consensus
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Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease 被引量:5
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作者 Domingo Balderramo 《World Journal of Gastroenterology》 SCIE CAS 2022年第47期6743-6751,共9页
Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcar... Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD. 展开更多
关键词 Inflammatory bowel disease Ulcerative colitis Crohn’s disease Dual-therapy biologic therapy small molecule drugs Clinical remission
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Construction of miRNA-mRNA regulatory network and drug prediction for ulcerative colitis associated colorectal cancer
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作者 Qing-Song Liu Shuang-Lan Chen +3 位作者 Yi Zhang Bin Li Zi-Yan Xie Shuai Xiong 《Medical Data Mining》 2021年第4期26-32,共7页
Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from t... Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer. 展开更多
关键词 Ulcerative colitis associated colorectal cancer miRNA-mRNA regulatory network small molecule drugs traditional Chinese medicine
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Expert opinion on translational research for advanced glioblastoma treatment 被引量:3
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作者 Xiaoteng Cui Yunfei Wang +2 位作者 Junhu Zhou Qixue Wang Chunsheng Kang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第5期344-352,共9页
Malignant gliomas are known to be one of the most difficult diseases to diagnose and treat because of the infiltrative growth pattern,rapid progression,and poor prognosis.Many antitumor drugs are not ideal for the tre... Malignant gliomas are known to be one of the most difficult diseases to diagnose and treat because of the infiltrative growth pattern,rapid progression,and poor prognosis.Many antitumor drugs are not ideal for the treatment of gliomas due to the blood-brain barrier.Temozolomide(TMZ)is a DNA alkylating agent that can cross the blood-brain barrier.As the only first-line chemotherapeutic drug for malignant gliomas at present,TMZ is widely utilized to provide a survival benefit;however,some patients are inherently insensitive to TMZ.In addition,patients could develop acquired resistance during TMZ treatment,which limits antitumor efficacy.To clarify the mechanism underlying TMZ resistance,numerous studies have provided multilevel solutions,such as improving the effective concentration of TMZ in tumors and developing novel small molecule drugs.This review discusses the in-depth mechanisms underlying TMZ drug resistance,thus aiming to provide possibilities for the establishment of personalized therapeutic strategies against malignant gliomas and the accelerated development and transformation of new targeted drugs. 展开更多
关键词 Malignant gliomas GLIOBLASTOMA TEMOZOLOMIDE CHEMORESISTANCE small molecule drugs
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Screening of Biomarkers for Hypertension Susceptibility in Pregnancy 被引量:1
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作者 Jian Xu Liye Fan +1 位作者 Feng Qi Xia Xiu 《Proceedings of Anticancer Research》 2020年第5期33-43,共11页
Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small m... Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small molecule drug-related lncRNAs.Methods:Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group.The placental tissues were taken from the patients.RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles;screening differentially expressed lncRNAs were used to predict target genes,and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways,respectively.Protein-protein interaction network,lncRNA-miRNAmRNA network,and differentially expressed genesmall molecule drug association networks were constructed.Results:RNA-seq analysis revealed 19 differentially expressed lncRNA(4 up-regulated;15 down-regulated)(P<0.05).Moreover,423 differentially expressed genes(DEGs)(84 up-regulated;339 downregulated)(P<0.05).GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage,inflammatory response,abnormal immune regulation,and abnormal trophoblast invasion.The PPI network and lncRNA-miRNA-mRNA network were constructed.Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs,mainly including antibody,inhibitor et al.Conclusion:Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional levelrelated signal pathways through targeted regulation of their target genes,and play an important role in the occurrence and development of gestational hypertension.The predicted small molecule drug can be used as a reference for clinical treatment. 展开更多
关键词 Gestational hypertension LncRNA Competitive endogenous RNA small molecule drug prediction
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