艾拉普林(Iclaprim) - 药物靶点：Bacterial DHFR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Iclaprim (USAN/INN)、Iclaprim Mesylate、AR-100

+ [5]

靶点

Bacterial DHFR

作用机制

Bacterial DHFR抑制剂(细菌二氢叶酸还原酶抑制剂)

治疗领域

感染皮肤和肌肉骨骼疾病呼吸系统疾病

在研适应症-

非在研适应症

复杂皮肤和皮肤结构感染医院获得性肺炎呼吸机相关性肺炎+ [3]

原研机构

F. Hoffmann-La Roche Ltd.

在研机构-

非在研机构

Motif Bio Plc

Arpida AG

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C19H22N4O3

InChIKeyHWJPWWYTGBZDEG-UHFFFAOYSA-N

CAS号192314-93-5

关联

10

项与艾拉普林相关的临床试验

PER-013-16

/ Completed临床3期

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, MULTICENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS ICLAPRIM VERSUS VANCOMYCIN IN THE TREATMENT OF ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS SUSPECTED OR CONFIRMED TO BE DUE TO GRAM-POSITIVE PATHOGENS. REVIVE-1

开始日期2016-06-16

申办/合作机构

Motif BioSciences, Inc.

EUCTR2015-002669-45-BG

/ Not yet recruiting临床3期

A Phase 3, randomized, double-blind, multicenter study to evaluate the safety and efficacy of intravenous iclaprim versus vancomycin in the treatment of acute bacterial skin and skin structure infections suspected or confirmed to be due to Gram-positive pathogens. REVIVE-1 - REVIVE-1

开始日期2016-05-09

申办/合作机构

Motif BioSciences, Inc.

EUCTR2015-002687-16-BE

/ Not yet recruiting临床3期

A Phase 3, randomized, double-blind, multicenter study to evaluate the safety and efficacy of intravenous iclaprim versus vancomycin in the treatment of acute bacterial skin and skin structure infections suspected or confirmed to be due to Gram-positive pathogens. REVIVE-1 - REVIVE-2

开始日期2016-04-02

申办/合作机构

Motif Bio Plc

100 项与艾拉普林相关的临床结果

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100 项与艾拉普林相关的转化医学

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100 项与艾拉普林相关的专利（医药）

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117

项与艾拉普林相关的文献（医药）

2024-12-01·APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

Anti-virulence potential of iclaprim, a novel folic acid synthesis inhibitor, against Staphylococcus aureus

Article

作者: Liu, Qingzhong ; Yang, Han ; Zhou, Jingwen ; Shu, Wen ; Song, Haoyue ; Hao, Lingyun ; He, Chunyan

Abstract:

Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen.

Key points:

• Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm• Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation• In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival

2024-12-01·Bioactive Materials

Unravelling the physicochemical and antimicrobial mechanisms of human serum albumin/tannic acid coatings for medical-grade polycaprolactone scaffolds

Article

作者: Donose, Bogdan C. ; Cometta, Silvia ; Dargaville, Tim R ; Rakić, Aleksandar D ; Juárez-Saldivar, Alfredo ; Dargaville, Tim R. ; Hutmacher, Dietmar W ; Donose, Bogdan C ; Ravichandran, Akhilandeshwari ; Hutmacher, Dietmar W. ; Xu, Yanan ; Bock, Nathalie ; Rakić, Aleksandar D.

Biofilm-related biomaterial infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation. To date, a large body of research can be reviewed for coatings which potentially prevent bacterial infection while promoting implant integration. Yet only a very small number has been translated from bench to bedside. This study provides an in-depth analysis of the stability, antibacterial mechanism, and biocompatibility of medical grade polycaprolactone (mPCL), coated with human serum albumin (HSA), the most abundant protein in blood plasma, and tannic acid (TA), a natural polyphenol with antibacterial properties. Molecular docking studies demonstrated that HSA and TA interact mainly through hydrogen-bonding, ionic and hydrophobic interactions, leading to smooth and regular assemblies. In vitro bacteria adhesion testing showed that coated scaffolds maintained their antimicrobial properties over 3 days by significantly reducing S. aureus colonization and biofilm formation. Notably, amplitude modulation-frequency modulation (AMFM) based viscoelasticity mapping and transmission electron microscopy (TEM) data suggested that HSA/TA-coatings cause morphological and mechanical changes on the outer cell membrane of S. aureus leading to membrane disruption and cell death while proving non-toxic to human primary cells. These results support this antibiotic-free approach as an effective and biocompatible strategy to prevent biofilm-related biomaterial infections.

2024-01-10·Antimicrobial agents and chemotherapy

Pharmacological validation of dihydrofolate reductase as a drug target in Mycobacterium abscessus

Article

作者: Dartois, Véronique A ; Aragaw, Wassihun Wedajo ; Bungard, Christopher J ; Marrouni, Abdellatif El ; Warrass, Ralf ; Olsen, David B ; Dick, Thomas ; Nickbarg, Elliott B ; Negatu, Dereje A

ABSTRACT:

The Mycobacterium abscessus drug development pipeline is poorly populated, with particularly few validated target-lead couples to initiate de novo drug discovery. Trimethoprim, an inhibitor of dihydrofolate reductase (DHFR) used for the treatment of a range of bacterial infections, is not active against M. abscessus . Thus, evidence that M. abscessus DHFR is vulnerable to pharmacological intervention with a small molecule inhibitor is lacking. Here, we show that the pyrrolo-quinazoline PQD-1, previously identified as a DHFR inhibitor active against Mycobacterium tuberculosis , exerts whole cell activity against M. abscessus . Enzyme inhibition studies showed that PQD-1, in contrast to trimethoprim, is a potent inhibitor of M. abscessus DHFR and over-expression of DHFR causes resistance to PQD-1, providing biochemical and genetic evidence that DHFR is a vulnerable target and mediates PQD-1’s growth inhibitory activity in M. abscessus . As observed in M. tuberculosis , PQD-1 resistant mutations mapped to the folate pathway enzyme thymidylate synthase (TYMS) ThyA. Like trimethoprim in other bacteria, PQD-1 synergizes with the dihydropteroate synthase (DHPS) inhibitor sulfamethoxazole (SMX), offering an opportunity to exploit the successful dual inhibition of the folate pathway and develop similarly potent combinations against M. abscessus . PQD-1 is active against subspecies of M. abscessus and a panel of clinical isolates, providing epidemiological validation of the target-lead couple. Leveraging a series of PQD-1 analogs, we have demonstrated a dynamic structure-activity relationship (SAR). Collectively, the results identify M. abscessus DHFR as an attractive target and PQD-1 as a chemical starting point for the discovery of novel drugs and drug combinations that target the folate pathway in M. abscessus .

4

项与艾拉普林相关的新闻（医药）

2023-01-25

·BioSpace

Methicillin-Resistant Staphylococcus aureus Infection Pipeline Clinical Trials Featuring 25+ companies

New York, USA, Jan. 25, 2023 (GLOBE NEWSWIRE) -- Methicillin-Resistant Staphylococcus aureus Infection Pipeline Clinical Trials Featuring 25+ companies| DelveInsight Methicillin-resistant Staphylococcus aureus (MRSA) is an infection caused by antibiotic-resistant strains of the pathogen Staphylococcus aureus. Rising incidence of Methicillin-resistant Staphylococcus aureus (MRSA) infections is creating health concerns among the population. Manufacturers are focusing on product development and launches for the treatment of Methicillin-resistant Staphylococcus aureus (MRSA). DelveInsight’s 'Methicillin-Resistant Staphylococcus aureus Infection Pipeline Insight 2023' report provides comprehensive global coverage of available, marketed, and pipeline methicillin-resistant Staphylococcusaureus infection therapies in various stages of clinical development. Major pharmaceutical companies are working to advance the pipeline space and future growth potential of the methicillin-resistant Staphylococcusaureus infection pipeline domain. Key Takeaways from the Methicillin-Resistant Staphylococcus aureus Infection Pipeline Report DelveInsight’s methicillin-resistant Staphylococcusaureus infection pipeline report depicts a robust space with 25+ companies and 28+ pipeline drugs for methicillin-resistant Staphylococcusaureus infection treatment. Key methicillin-resistant Staphylococcusaureus infection companies include Trellis Bioscience, LegoChem Biosciences, Aptorum Group, ContraFect, Crystalgenomics, Cellics Therapeutics, MicuRx, Oxford Antibiotic Group, Destiny Pharma, TSRL, Inc., TAXIS Pharmaceuticals, Basilea Pharmaceutica, Helperby Therapeutics, Akagera Medicines, Histogen, Alphamab Co. Ltd, Biocidium Pharmaceuticals, and others are evaluating novel methicillin-resistant Staphylococcusaureus infection drugs candidate to improve the treatment landscape. Promising methicillin-resistant Staphylococcusaureus infection pipeline therapies in various stages of development include TRL1068, Delpazolid, ALS 4, Teicoplanin inhalation, CG 400549, SAAP 148, Exebacase, Marinus, CTI 005, Iclaprim, MRX 4, MRX 7, XF-73, TXA709, ARV-1801, ACX-375C, ABX-605, IBT-V02, BCM-0184, Contezolid, TetramOX, Ceftobiprole, HY-004B8b, HY-005B8a, CG-549, Emricasan, KN043, and several others. Ceftobiprole medocaril, the prodrug of the active moiety ceftobiprole, is a cephalosporin antibiotic for intravenous administration, with rapid bactericidal activity against a wide range of Gram-positive and Gram-negative bacteria. This includes methicillin-susceptible and resistant Staphylococcus aureus (MSSA, MRSA) and susceptible Pseudomonas spp. In October 2022, Basilea Pharmaceutica announced the results from Phase III ERADICATE study, evaluating ceftobiprole in the treatment of adult patients with bacterial bloodstream infections caused by Staphylococcus aureus. Results for the primary efficacy outcomes were consistent in key subgroups including in patients with MSSA or MRSA bloodstream infections at baseline, and in various categories of underlying conditions such as skin and skin structure infections, abdominal abscesses, chronic dialysis, septic arthritis, osteomyelitis, definite right-sided infective endocarditis and in patients with persistent SAB. Basilea also planned to submit a New Drug Application (NDA) for ceftobiprole to the US Food and Drug Administration (FDA) around year-end 2022. Exebacase (CF-301) being developed by ContraFect Corporation is a lysin with potent activity against Staphylococcus aureus ("Staph aureus"). Exebacase has the potential to be the first-in-class of a new treatment for patients with Staph aureus bacteremia. The FDA has granted Breakthrough Therapy designation to exebacase for the treatment of MRSA bloodstream infections (bacteremia), including right-sided endocarditis, when used in addition to SOC antistaphylococcal antibiotics in adult patients, based on the final data from the Phase II superiority trial of exebacase. In July 2022, Destiny Pharma plc announced that it had received an award from the Cystic Fibrosis Foundation. The research project will establish the potential of the Company’s proprietary XF-73 drug as a novel treatment for cystic fibrosis patients infected with methicillin-resistant Staphylococcus aureus (MRSA). CTI-005 is for the treatment of Methicillin Resistance Staphylococcus Aureus (MRSA) Pneumonia and has been granted IND allowance from the US FDA. The potent RBC-NS has the membrane lipids and receptors that a normal red blood cell has, however, the high surface-volume ratio of the RBC-NS allows it to act as a decoy. This characteristic allows the RBC-NS to bind and neutralize toxins, auto-antibodies, and bacterial infections. The pore-forming toxins emitted by MRSA can be effectively absorbed and neutralized by RBC-NS. Request a sample and discover the recent advances in methicillin-resistant Staphylococcusaureus infection treatment drugs @ Methicillin-Resistant Staphylococcus aureus Infection Pipeline Report The methicillin-resistant Staphylococcusaureus infection pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage methicillin-resistant Staphylococcusaureus infection products, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the methicillin-resistant Staphylococcusaureus infection pipeline landscape. Methicillin-Resistant Staphylococcus aureus Infection Overview Methicillin-resistant Staphylococcus aureus (MRSA) infections are caused by bacteria that have attained resistance from several antibiotics that treat diseases caused by Staphylococcus bacteria. The common patients of Methicillin-resistant Staphylococcus aureus (MRSA) infections are patients that have been in hospitals or healthcare settings for a long duration where the bacteria is found commonly. MRSA infections are known as healthcare-associated MRSA (HA-MRSA) if infected in hospitals. Such infections can spread to healthcare workers through invasive procedures, which are further transmitted to several patients by touching and operating with bare hands. Other MRSA infections occur in a considerable population of healthy people. People associated with community-associated MRSA (CA-MRSA) show symptoms appearing as painful skin boils. It further spreads through physical contact between individuals. The population at higher risk includes people surrounded by a significant number of people and childcare workers. MRSA infections might look like red bumps, pimples, or spider bites, accompanied by pus and fever. Find out more about methicillin-resistant Staphylococcusaureus infection treatment drugs @ Drugs for Methicillin-Resistant Staphylococcus aureus Infection Treatment A snapshot of the Methicillin-Resistant Staphylococcus aureus Infection pipeline drugs mentioned in the report: Drug Company Phase MoA RoA Ceftobiprole Basilea Pharmaceutica Phase III Cell wall inhibitors; Peptidyltransferase inhibitors Intravenous CG 549 CrystalGenomics Phase II Enoyl-ACP reductase inhibitors; Fatty acid synthase expression inhibitors; Fatty acid synthetase complex inhibitors Oral BCM-0184 Biocidium Pharmaceuticals Phase I NA Oral/Topical TRL1068 Trellis Bioscience Phase I Bacterial biofilm inhibitors Intravenous ALS 4 Aptorum Group Phase I Bacterial virulence inhibitors Oral EVX-B1 Evaxion Biotech Preclinical Immunostimulants NA Emricasan Histogen Preclinical Apoptosis inhibitors; Caspase inhibitors NA TarO inhibitor Prokaryotics Discovery Cell membrane inhibitors; Cell wall inhibitors NA Learn more about the emerging methicillin-resistant Staphylococcusaureus infection pipeline therapies @ Methicillin-Resistant Staphylococcus aureus Infection Clinical Trials Methicillin-Resistant Staphylococcus aureus Infection Therapeutics Assessment The methicillin-resistant Staphylococcus aureus infection pipeline report proffers an integral view of methicillin-resistant Staphylococcusaureus infection emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Methicillin-Resistant Staphylococcus aureus Infection Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Pre-clinical, Discovery, Discontinued, Inactive, Phase I, Phase II, Phase III Therapeutics AssessmentBy Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical. Therapeutics AssessmentBy Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Therapeutics AssessmentBy Mechanism of Action: Cell wall inhibitors; Peptidyltransferase inhibitors, Enoyl-ACP reductase inhibitors; Fatty acid synthase expression inhibitors; Fatty acid synthetase complex inhibitors, Bacterial biofilm inhibitors, Bacterial virulence inhibitors, Immunostimulants, Apoptosis inhibitors; Caspase inhibitors, Cell membrane inhibitors; Cell wall inhibitors Key Methicillin-Resistant Staphylococcus aureus Infection Companies: Trellis Bioscience, LegoChem Biosciences, Aptorum Group, ContraFect, Crystalgenomics, Cellics Therapeutics, MicuRx, Oxford Antibiotic Group, Destiny Pharma, TSRL, Inc., TAXIS Pharmaceuticals, Basilea Pharmaceutica, Helperby Therapeutics, Akagera Medicines, Histogen, Alphamab Co. Ltd, Biocidium Pharmaceuticals, and others. Key Methicillin-Resistant Staphylococcus aureus Infection Pipeline Therapies: TRL1068, Delpazolid, ALS 4, Teicoplanin inhalation, CG 400549, SAAP 148, Exebacase, Marinus, CTI 005, Iclaprim, MRX 4, MRX 7, XF-73, TXA709, ARV-1801, ACX-375C, ABX-605, IBT-V02, BCM-0184, Contezolid, TetramOX, Ceftobiprole, HY-004B8b, HY-005B8a, CG-549, Emricasan, KN043, and others. Dive deep into rich insights for new drugs for methicillin-resistant Staphylococcusaureus infection treatment; visit @ Methicillin-Resistant Staphylococcus aureus Infection Drugs Table of Contents 1. Methicillin-Resistant Staphylococcus aureus Infection Pipeline Report Introduction 2. Methicillin-Resistant Staphylococcus aureus Infection Pipeline Report Executive Summary 3. Methicillin-Resistant Staphylococcus aureus Infection Pipeline: Overview 4. Analytical Perspective In-depth Commercial Assessment 5. Methicillin-Resistant Staphylococcus aureus Infection Pipeline Therapeutics 6. Methicillin-Resistant Staphylococcus aureus Infection Pipeline: Late Stage Products (Pre-registration) 7. Methicillin-Resistant Staphylococcus aureus Infection Pipeline: Late Stage Products (Phase III) 7.1 Ceftobiprole: Basilea Pharmaceutica 8. Methicillin-Resistant Staphylococcus aureus Infection Pipeline: Mid Stage Products (Phase II) 8.1 CG549: CrystalGenomics 9. Methicillin-Resistant Staphylococcus aureus Infection Pipeline: Early Stage Products (Phase I) 9.1 TRL1068: Trellis Bioscience 10. Methicillin-Resistant Staphylococcus aureus Infection Pipeline Therapeutics Assessment 11. Inactive Products in the Methicillin-Resistant Staphylococcus aureus Infection Pipeline 12. Company-University Collaborations (Licensing/Partnering) Analysis 13. Key Companies 14. Key Products in the Methicillin-Resistant Staphylococcus aureus Infection Pipeline 15. Unmet Needs 16. Market Drivers and Barriers 17. Future Perspectives and Conclusion 18. Analyst Views 19. Appendix For further information on the methicillin-resistant Staphylococcusaureus infection pipeline therapeutics, reach out @ Methicillin-Resistant Staphylococcus aureus Infection Treatment Drugs Related Reports Methicillin-Resistant Staphylococcus aureus Epidemiology Forecast Methicillin-Resistant Staphylococcus aureus Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and the methicillin-resistant Staphylococcusaureus epidemiology trends. Methicillin-Resistant Staphylococcus aureus Infection Market Methicillin-Resistant Staphylococcus aureus Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key methicillin-resistant Staphylococcusaureus infection companies, including Trellis Bioscience, LegoChem Biosciences, Aptorum Group, Allergan, iNtRON Biotechnology, Neupharma, ImmuPharma, Lytix Biopharma, CrystalGenomics, AIMM Therapeutics, among others. Staphylococcus aureus Bacteremia Pipeline Staphylococcus aureus Bacteremia Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug pro including clinical and non-clinical stage products, and the key Staphylococcus aureus Bacteremia companies, including ContraFect, Armata Pharmaceuticals, iNtRON Biotechnology, Durata Therapeutics, Cipher Pharmaceuticals, XBiotech, Basilea Pharmaceutica, Genentech, among others. Hospital Acquired Methicillin-Resistant Staphylococcus aureus Infections Pipeline Hospital Acquired Methicillin-Resistant Staphylococcus aureus Infections Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug pro including clinical and non-clinical stage products, and the key Hospital Acquired Methicillin-Resistant Staphylococcus aureus Infections companies, including Trellis Bioscience, LegoChem Biosciences, Aptorum Group, Allergan, iNtRON Biotechnology, Neupharma, ImmuPharma, Lytix Biopharma, CrystalGenomics, AIMM Therapeutics, among others. 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Connect with us atLinkedIn Contact Us Shruti Thakur info@delveinsight.com +1(919)321-6187

临床3期临床2期临床结果

2022-10-30

·医药地理

精英荟萃 | 深化产学研，推动多方共赢化学原料药绿色发展

10月29日，2022中国医药工业大会暨《中国医药工业杂志》学术年会期间，由中国医药工业研究总院、医药先进制造国家工程研究中心、创新药物与制药工艺国家重点实验室和中国医药工业信息中心共同主办，《中国医药工业杂志》承办的“原料药化学合成与绿色制药论坛”在上海顺利召开。本次会议采用线上与线下相结合的形式，邀请了医药研发和医药工业制造领域的专家共议产业难点破解之策。担任本场论坛主席的中国工程院院士陈芬儿以“Stereocontrolled Total Synthesis of Prostaglandins-From Organocatalysis to Biocatalysis and to Streamlined Process”为题分享了他的学术成果。陈院士指出，构建前列腺素（PGs）类重要中间体corey lactone的立体中心以合成PGFs化学结构具有相当大的难度，他的课题组通过运用三种前列腺素的通用合成方法，包括手性诱导前列腺素的不对称硼氢化、前列腺素手性螺旋-磷酸和直接选择性伯醇氧化有机催化Baeyer-Villiger氧化（B-V氧化）、B-V氧化组合酮还原酶生物催化还原前列腺素的烯酮。该优化工艺具备工业化规模应用的潜力，能为前列腺高立体的选择性合成提供良好基础。长三角绿色制药协同创新中心执行主任、教授苏为科通过连线方式向与会者们分享了“基于人工智能的连续流药物合成技术与装备开发”的报告。他表示，AI技术可以加快新药研发进程，未来将实现对传统制药行业的颠覆。近年来，智能制药研究成果不断涌现，从而让制药装备面临着挑战和机遇，日益减少的化石能源和原料、环保压力和化工危险工艺等问题，让智能药物制造机器人和制药过程本质安全化备受重视和发展。在随后的演讲中，苏教授介绍了如何实现药物合成智能化和连续流反应的案例，并对连续流制药和智能制药的未来作了展望。中国医药工业研究总院研究员周伟澄分享了主题为“仿制药（抢仿）的创新合成”的精彩报告。他指出，医药工业和药物生产涉及药物化学合成和制药工艺合成两方面，化合物专利到期即为仿制药，但原研药公司还拥有该药物的合成工艺专利，而化合物专利中的药化合成，往往难以工业化，因此，抢占仿制药必须开发新的药物合成工艺。周伟澄研究员分别以磷酸特地唑胺、艾拉普林和Mavorrixafor三个药物为例，分享了如何回避原研药专利的工艺路线，从而实现仿制药（抢仿）的创新合成新思路。上海现代制药股份有限公司研究院院长倪峰就“绿色合成工程技术在药物开发中的应用”作了主题报告。手性药物可通过传统拆分和手性合成两种方式来获得，两者各有优劣，而绿色手性合成技术则刚好可将两种方式的优点进行整合，兼备产率高、选择性高、工序步骤简洁、工艺可操作性强、无需额外催化剂和拆分剂等特点。倪院长着重讲述了晶体诱导动态动力学拆分（CIDR）和晶体诱导的不对称转化（CIAT）两种动态动力学手性合成技术的应用，并强调CIDR和CIAT成功的条件需要同时满足动态平衡的建立和优势途径的建立。中国医药工业研究总院研究员张福利分享了“绿色制药理念及案例分析”的主题报告。他认为，目前各种技术是实现绿色制药的一种手段，而工艺改进的理念是用最小的代价达到预期的目的，其任务是改进老产品的生产工艺，为新产品寻找一个较理想的技术路线，将工艺改进做到极致就是实现绿色化学。将工艺改进“越做越简单”离不开工艺创新、原始创新和系统思维，他分别以“糖精工艺改进”、“氢负理论”为例解读了自己对工艺创新和原始创新的理解，并强调了两种创新模式都需要贯穿系统性思维，找到巧妙的解决之道。山东大学药学院常务副院长、教授方浩围绕“抗肿瘤创新药物研发”的主题作了相关分享。恶性肿瘤是威胁人类健康的重大疾病，从全球药物研发管线适应证类别统计数和FDA过去31年审批上市的抗肿瘤药物大数据来看，抗肿瘤药物占比最高。抗肿瘤药物治疗当前面临的挑战主要有药物耐药、免疫微环境、难成药靶标、肿瘤异质性等。随后，方教授分享了其课题组针对组蛋白去乙酰化酶（HDACs）的研究，分别从HDAC抑制剂克服药物耐药、提高实体肿瘤疗效、激活肿瘤免疫等方面举例了通过新方法和新技术靶向让传统药物具备新的应用场景。武汉工程大学教授古双喜就“磷酸酯类前药的工业化合成技术研究与开发“作了系统的讲解。古教授指出，磷酸酯类前药在药物设计与开发中可实现提高水溶性、提高脂溶性、提高药物的安全性（治疗指数）、改善药物代谢动力学性质从而提高生物利用度、改善药物代谢动力学性质从而提高药物稳定性等应用。他以氟苯尼考磷酸单酯和泼尼松及其磷酸酯为例，讲述了课题组如何利用一锅法成功制备氟苯尼考磷酸二酯、雌酮磷酸酯、刺芒柄花素磷酸酯等前药的合成工艺，并基于这些磷酸酯类前药改善传统药物治疗的效果。上海药品审评核查中心高级审评员周一萌为与会者带来了“新版药品管理法实施后化学原料药关联审评的解析”专题报告。随着新药品管理法、注册管理办法、MAH制度、药品注册审评等一系列新制度，尤其是原辅包生产企业实施原辅包的关联审评制度正式发布，制剂企业和原辅包生产企业都面临着新的机遇和挑战。原料药成为药品的一种活性成分，从研发立项到注册申报再到上市，涉及多种因素进行磨合靠拢。周一萌审评员详细梳理和解读了相关制度和政策演变，从监管的视角为原料药化学工艺合成提供了一个优化建议。论坛上、下半场分别由中国医药工业研究总院研究员张福利和中国医药工业研究总院科研部部长蔡正艳主持。END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

仿制药专利到期创新药

2022-10-29

·医药地理

以产业创新为驱动、以临床需求为导向

10月29日，2022中国医药工业大会暨《中国医药工业杂志》学术年会期间，由中国医药工业研究总院、医药先进制造国家工程研究中心、创新药物与制药工艺国家重点实验室和中国医药工业信息中心共同主办，《中国医药工业杂志》承办的“原料药化学合成与绿色制药论坛”在上海顺利召开。本次会议采用线上与线下相结合的形式，邀请了医药研发和医药工业制造领域的专家共议产业难点破解之策。担任本场论坛主席的中国工程院院士陈芬儿以“Stereocontrolled Total Synthesis of Prostaglandins-From Organocatalysis to Biocatalysis and to Streamlined Process”为题分享了他的学术成果。陈院士指出，构建前列腺素（PGs）类重要中间体corey lactone的立体中心以合成PGFs化学结构具有相当大的难度，他的课题组通过运用三种前列腺素的通用合成方法，包括手性诱导前列腺素的不对称硼氢化、前列腺素手性螺旋-磷酸和直接选择性伯醇氧化有机催化Baeyer-Villiger氧化（B-V氧化）、B-V氧化组合酮还原酶生物催化还原前列腺素的烯酮。该优化工艺具备工业化规模应用的潜力，能为前列腺高立体的选择性合成提供良好基础。长三角绿色制药协同创新中心执行主任、教授苏为科通过连线方式向与会者们分享了“基于人工智能的连续流药物合成技术与装备开发”的报告。他表示，AI技术可以加快新药研发进程，未来将实现对传统制药行业的颠覆。近年来，智能制药研究成果不断涌现，从而让制药装备面临着挑战和机遇，日益减少的化石能源和原料、环保压力和化工危险工艺等问题，让智能药物制造机器人和制药过程本质安全化备受重视和发展。在随后的演讲中，苏教授介绍了如何实现药物合成智能化和连续流反应的案例，并对连续流制药和智能制药的未来作了展望。中国医药工业研究总院研究员周伟澄分享了主题为“仿制药（抢仿）的创新合成”的精彩报告。他指出，医药工业和药物生产涉及药物化学合成和制药工艺合成两方面，化合物专利到期即为仿制药，但原研药公司还拥有该药物的合成工艺专利，而化合物专利中的药化合成，往往难以工业化，因此，抢占仿制药必须开发新的药物合成工艺。周伟澄研究员分别以磷酸特地唑胺、艾拉普林和Mavorrixafor三个药物为例，分享了如何回避原研药专利的工艺路线，从而实现仿制药（抢仿）的创新合成新思路。上海现代制药股份有限公司研究院院长倪峰就“绿色合成工程技术在药物开发中的应用”作了主题报告。手性药物可通过传统拆分和手性合成两种方式来获得，两者各有优劣，而绿色手性合成技术则刚好可将两种方式的优点进行整合，兼备产率高、选择性高、工序步骤简洁、工艺可操作性强、无需额外催化剂和拆分剂等特点。倪院长着重讲述了晶体诱导动态动力学拆分（CIDR）和晶体诱导的不对称转化（CIAT）两种动态动力学手性合成技术的应用，并强调CIDR和CIAT成功的条件需要同时满足动态平衡的建立和优势途径的建立。中国医药工业研究总院研究员张福利分享了“绿色制药理念及案例分析”的主题报告。他认为，目前各种技术是实现绿色制药的一种手段，而工艺改进的理念是用最小的代价达到预期的目的，其任务是改进老产品的生产工艺，为新产品寻找一个较理想的技术路线，将工艺改进做到极致就是实现绿色化学。将工艺改进“越做越简单”离不开工艺创新、原始创新和系统思维，他分别以“糖精工艺改进”、“氢负理论”为例解读了自己对工艺创新和原始创新的理解，并强调了两种创新模式都需要贯穿系统性思维，找到巧妙的解决之道。山东大学药学院常务副院长、教授方浩围绕“抗肿瘤创新药物研发”的主题作了相关分享。恶性肿瘤是威胁人类健康的重大疾病，从全球药物研发管线适应证类别统计数和FDA过去31年审批上市的抗肿瘤药物大数据来看，抗肿瘤药物占比最高。抗肿瘤药物治疗当前面临的挑战主要有药物耐药、免疫微环境、难成药靶标、肿瘤异质性等。随后，方教授分享了其课题组针对组蛋白去乙酰化酶（HDACs）的研究，分别从HDAC抑制剂克服药物耐药、提高实体肿瘤疗效、激活肿瘤免疫等方面举例了通过新方法和新技术靶向让传统药物具备新的应用场景。武汉工程大学教授古双喜就“磷酸酯类前药的工业化合成技术研究与开发“作了系统的讲解。古教授指出，磷酸酯类前药在药物设计与开发中可实现提高水溶性、提高脂溶性、提高药物的安全性（治疗指数）、改善药物代谢动力学性质从而提高生物利用度、改善药物代谢动力学性质从而提高药物稳定性等应用。他以氟苯尼考磷酸单酯和泼尼松及其磷酸酯为例，讲述了课题组如何利用一锅法成功制备氟苯尼考磷酸二酯、雌酮磷酸酯、刺芒柄花素磷酸酯等前药的合成工艺，并基于这些磷酸酯类前药改善传统药物治疗的效果。上海药品审评核查中心高级审评员周一萌为与会者带来了“新版药品管理法实施后化学原料药关联审评的解析”专题报告。随着新药品管理法、注册管理办法、MAH制度、药品注册审评等一系列新制度，尤其是原辅包生产企业实施原辅包的关联审评制度正式发布，制剂企业和原辅包生产企业都面临着新的机遇和挑战。原料药成为药品的一种活性成分，从研发立项到注册申报再到上市，涉及多种因素进行磨合靠拢。周一萌审评员详细梳理和解读了相关制度和政策演变，从监管的视角为原料药化学工艺合成提供了一个优化建议。论坛上、下半场分别由中国医药工业研究总院研究员张福利和中国医药工业研究总院科研部部长蔡正艳主持。END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

仿制药专利到期创新药

100 项与艾拉普林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08337	艾拉普林	J01EA03	DB06358

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
皮肤和皮肤结构感染	临床3期	美国	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	保加利亚	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	智利	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	哥伦比亚	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	德国	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	拉脱维亚	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	秘鲁	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	波兰	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	波多黎各	Motif Bio Plc	2015-11-01
皮肤和皮肤结构感染	临床3期	乌克兰	Motif Bio Plc	2015-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02600611 \| NCT02607618 (REVIVE-1 and REVIVE-2, Pubmed \| Int J Antimicrob Agents)	临床3期	皮肤和皮肤结构感染	-	Iclaprim 80 mg	糧觸憲襯壓廠鹹鬱膚襯(鑰夢憲遞構憲製窪積鏇) = 願蓋衊網廠淵築範蓋廠鹽遞憲廠餘製醖襯糧窪 (窪網積糧淵範網積膚鬱 )	积极	2018-08-01
				Vancomycin 15 mg/kg	糧觸憲襯壓廠鹹鬱膚襯(鑰夢憲遞構憲製窪積鏇) = 憲蓋膚遞蓋鹽餘壓選遞鹽遞憲廠餘製醖襯糧窪 (窪網積糧淵範網積膚鬱 )
NCT02607618 (REVIVE-2, CTgov)	临床3期	皮肤结构和软组织感染	613	Iclaprim (Iclaprim)	選網衊廠艱廠獵糧餘糧(蓋蓋蓋鏇鬱齋網襯醖壓) = 築襯網繭糧醖顧窪遞鹽窪憲築鑰網窪願餘鹽艱 (壓觸觸糧獵夢夢築觸鹽, 製膚淵製觸鏇蓋繭鹹膚 ~ 築遞選鬱觸範壓構繭積) 更多	-	2018-07-11
				Vancomycin (Vancomycin)	選網衊廠艱廠獵糧餘糧(蓋蓋蓋鏇鬱齋網襯醖壓) = 醖願壓簾壓淵觸鏇糧廠窪憲築鑰網窪願餘鹽艱 (壓觸觸糧獵夢夢築觸鹽, 齋構醖製鬱鏇憲醖網鹹 ~ 選繭築鏇鹹網廠願網願) 更多
NCT02600611 (REVIVE-1, CTgov)	临床3期	皮肤结构和软组织感染 \| 皮肤和皮肤结构感染	600	iclaprim (Iclaprim)	夢壓糧遞餘製餘積觸選(遞範膚鹽選醖選醖淵構) = 鑰選構範壓簾襯淵餘繭衊糧繭繭齋觸窪夢淵鏇 (築鑰積糧艱糧範選壓範, 選鹹簾製鹽壓蓋齋窪願 ~ 衊壓醖製獵範簾積願憲) 更多	-	2018-06-19
				Vancomycin (Vancomycin)	夢壓糧遞餘製餘積觸選(遞範膚鹽選醖選醖淵構) = 網壓繭構齋糧顧鹹憲齋衊糧繭繭齋觸窪夢淵鏇 (築鑰積糧艱糧範選壓範, 觸艱衊鹽鏇蓋鏇衊鬱窪 ~ 膚襯顧窪窪顧蓋膚夢製) 更多
NCT02607618 (REVIVE-2, Pubmed \| Antimicrob Agents Chemother) 人工标引	临床3期	皮肤和皮肤结构感染	613	Intravenous Iclaprim	鹽製簾窪憲憲鏇積膚製(艱艱遞選鑰繭繭齋廠選) = 憲獵醖膚餘醖艱遞鬱願蓋簾醖繭膚廠襯餘鏇淵 (衊鏇簾鬱觸鹽製鏇鹽積 )	非优	2018-04-26
				Vancomycin	鹽製簾窪憲憲鏇積膚製(艱艱遞選鑰繭繭齋廠選) = 鏇選憲鏇繭壓艱選夢獵蓋簾醖繭膚廠襯餘鏇淵 (衊鏇簾鬱觸鹽製鏇鹽積 )