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An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China division for medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

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Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

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World Journal of Diabetes 2024年第3期15卷 572-574页

作者： Asis Bala pharmacology and Drug Discovery Research Laboratory Division of Life SciencesInstitute of Advanced Study in Science and TechnologyGuwahati 781035AssamIndia

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling *** effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of *** oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

关键词： Diabetes Cardiovascular complication Advanced glycation end products Reactive oxygen species Reactive nitrogen species Peroxynitrite

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A Comprehensive Review on Preclinical Safety and Toxicity of medicinal Plants

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Clinical Complementary Medicine and pharmacology 2024年第1期4卷 95-111页

作者： Madhav Nilakanth Mugale Kapil Dev Bhumika S.More Vaishali Sunil Mishra Kaveri R.Washimkar Kishan Singh Rakesh Maurya Srikanta Kumar Rath Debprasad Chattopadhyay Naibedya Chattopadhyay division of Toxicology and Experimental Medicine CSIR-Central Drug Research Institute(CSIR-CDRI)Lucknow 226031India division of Phytochemistry CSIR-Central Institute of Medicinal and Aromatic Plants(CSIR-CIMAP)Lucknow 226015India medicinal and Process chemistry division CSIR-CDRI Lucknow 226031India division of Endocrinology CSIR-CDRI Lucknow 226031India division of Ethnomedicine ICMR-National Institute of Traditional MedicineNehru NagarBelagavi 590010and ICMR-Virus UnitKolkata 700010India Department of Health Research NSHM Knowledge CampusKolkata 700051India

Background:Globally,80%people use plant-derived products for treating or preventing *** prevalent perception about medicinal plants is that they are safe and devoid of adverse ***,approximately 1,50,000 plants contain toxic ***:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral ***:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of ***:The studies included were performed in rodents,and the test substances were administered *** search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been *** a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity ***:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety ***,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.

关键词： Extract Herbal medicine Toxicity Rodent Secondary metabolite

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Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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Synthesis of N-substituted-2-aminobenzothiazoles using nano copper oxide as a recyclable catalyst under ligand-free conditions in reusable PEG-400 medium

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Chinese Chemical Letters 2014年第5期25卷 732-736页

作者： Satish Gaddam Harshavardhan Reddy Kasireddy Karnakar Konkala Ramesh Katla Nageswar Yadavalli Venkata Durga CSIR-medicinal chemistry and pharmacology division Indian Institute of Chemical Technology

A simple and practical method for the synthesis of N-substituted-2-aminobenzothiazoles via a crosscoupling reaction of 2-iodo anilines with isothiocyanates is envisaged using nano copper oxide as a recyclable catalyst and Cs2CO3as a base in PEG-400,as a bio-degradable,reusable,inexpensive and nontoxic reaction medium,under ligand-free *** present tandem process underlines environmental acceptability to access a wide range of N-substituted-2-aminobenzothiazoles in good to excellent yields.

关键词： 2-Aminobenzothiazoles 2-Iodoanilines Isothiocyanates CuO nanoparticles Recyclability PEG-400

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Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Pathology division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Experimental Medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy Department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,Ppharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

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Antiarrhythmic ionic mechanism of Guanfu base A—Selective inhibition of late sodium current in isolated ventricular myocytes from guinea pigs

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Chinese Journal of Natural Medicines 2015年第5期13卷 361-367页

作者： JIN Si-Si GUO Qiao XU Jing YU Peng LIU Jing-Han TANG Yi-Qun Research division of pharmacology China Pharmaceutical University Department of Natural medicinal chemistry China Pharmaceutical University

The present study was designed to determine the effects of Guanfu base A(GFA) on the late sodium current(INa.L),transient sodium current(INa.T),HERG current(IHERG),and Kv1.5 current(IKv1.5).The values of INa.L,INa.T,IHERG and IKv1.5 were recorded using the whole-cell patch clamp *** with other channels,GFA showed selective blocking activity in late sodium *** inhibited INa.L in a concentration-dependent manner with an IC50 of(1.57 ± 0.14) μmol·L-1,which was significantly lower than its IC50 values of(21.17 ± 4.51) μmol·L-1 for the *** inhibitory effect of GFA on INa,L was not affected by 200μmol·L-1 *** inhibited IHERG with an IC50 of(273 ± 34) μmol·L-1 and has slight blocking effect on IKv1.5,decreasing IKv1.5 by only 20.6% at 200 μmol·*** summary,GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species..These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.

关键词： Guanfu base A Late sodium current Transient sodium current Kv1.5 current Arrhythmia

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China division of Hematology&Oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

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Comparison of conventional and supported liquid extraction methods for the determination of sitagliptin and simvastatin in rat plasma by LC-ESI-MS/MS

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Journal of Pharmaceutical Analysis 2015年第3期5卷 161-168页

作者： B.Ramesh N.Manjula S.R.Bijargi V.U.M.Sarma P.Sita Devi Natural Products chemistry division Indian Institute of Chemical Technology medicinal chemistry & pharmacology division Indian Institute of Chemical Technology

Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC-MS/MS, including （1） liquid-liquid extraction （LLE）, （2） solid phase extraction （SPE） and （3） supported liquid extraction （SLE）. Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring （MRM） in a positive ion mode with ESI. The transitions monitored were m./z 441.1→325.2 for simvastatin, 408.2→235.1 for sitagliptin and 278.1→260.1 for the IS. The lower limit of quantification （LLOQ） was 0.2 ng/mL for sitagliptin and 0.1 ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies.

关键词： Rat plasma Simvastatin Sita#'ptin Supported liquid extraction

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Paternal mixed exposure to nicotine/ethanol/caffeine damaged cartilage quality in paternal/offspring rats and its differential glucocorticoid regulation mechanisms

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Food Science and Human Wellness 2024年

作者： Yi Liu Hao Xiao Yi Liu Bin Li Hui Wang Liaobin Chen division of Joint Surgery and Sports Medicine， Department of Orthopedic Surgery， Zhongnan Hospital of Wuhan University Hubei Provincial Key Laboratory of Developmentally Originated Disease Joint Disease Research Center of Wuhan University Department of pharmacology， Wuhan University School of Basic Medical Sciences

Nicotine， ethanol， and caffeine are the most common exogenous substances in the men’s living environment， but their effects on the cartilage quality in the father and offspring have not been reported. According to the average daily intake of adult men， we constructed a male rat model of paternal mixed exposure (PME) to low-dose nicotine (0.1 mg/kg.d)， ethanol (0.5 g/kg.d)， and caffeine (7.5 mg/kg.d) for 8 weeks. Then， the male rats mated with normal female rats to obtain offspring. The results showed that PME reduced the cartilage quality of paternal and offspring rats. Among them， the paternal cartilage was damaged by enhancing matrix degradation， while the offspring cartilage was damaged by reducing matrix synthesis. The cartilage damage in male offspring rats was more evident than in female offspring. It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME. In addition， the sex hormone receptor AR and ERβ mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300. This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.

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