Eserine Salicylate

IRVING, Texas--( BUSINESS WIRE )--The End Drug Shortages Alliance (EDSA) today released a report assessing the impact to the U.S. market caused by the recent closure of a drug manufacturer. Akorn Pharmaceuticals filed for bankruptcy Feb. 23 and ceased all U.S. manufacturing operations, leaving questions about the impact to the supply of over 100 medications — some essential — including injectable and oral products as well as ophthalmic, otic and topical formulations. The full report may be accessed here . The EDSA report, which was a collaborative effort among Vizient, ASHP, and Children’s Hospital Association (CHA), provides an analysis for products with greatest risk of supply disruption and vulnerability, including four essential medications, that, if not available, would prove the greatest threat to a hospital’s ability to provide immediate and high-quality patient care. As clinicians will need to develop strategies for potential drug shortages, the report offers high-level guidance, including for the impacted essential medications such as adenosine, used in the treatment of supraventricular tachycardia; calcitriol, used to manage hyperparathyroidism in patients undergoing renal dialysis; dimercaprol, an antidote for metal poisoning; mycophenolate mofetil, a prophylaxis for organ rejection; and physostigmine, used in the reversal of anticholinergic syndrome. “Transparency regarding drug shortages is important to ensure patient care remains uninterrupted,” said Mittal Sutaria, senior vice president, Vizient pharmacy contract and program services and EDSA board member. “The healthcare system needs time so that pharmaceutical companies can increase manufacturing when possible and providers can develop mitigation strategies to alleviate any potential disruption in supply when a manufacturer exits the market.” The report assesses data from multiple sources including essential medication status, market share and current ASHP shortage designation to estimate the resilience of a particular product. It also offers recommendations for key stakeholders, including: Manufacturers and wholesalers, to evaluate their ability to maintain or increase product availability or manufacture products for which Akorn was the sole supplier and establish protective allocations to ensure medications are available for patient care. Group purchasing organizations, to pursue novel sourcing strategies and emergency contracting for life-saving medications. Clinicians and providers, to exercise a stewardship mindset and review purchasing and formulary status to determine conservation and mitigation strategies. “The more time providers and the broader health care system have to prepare for a shortage, the better,” said Eric Tichy, division chair, pharmacy supply solutions for Mayo Clinic and EDSA chairperson. “Advance knowledge of supply disruptions is part of the transparency that the End Drug Shortages Alliance has advocated for since forming. Transparency benefits all market participants.” About End Drug Shortages Alliance The End Drug Shortages Alliance is a collaboration of health care industry stakeholders, including providers, group purchasing organizations, manufacturers, distributors and other industry thought leaders dedicated to solving the pharmaceutical supply challenges that disrupt access to essential medications in the U.S. We prioritize initiatives focused on transparency, quality, redundancy and production of additional supply to achieve undisrupted access to essential medications for health care providers and patients.

近日，上海交大瞿旭东团队受邀在天然产物研究领域权威期刊Natural Product Reports发表题为《Biosynthesis of pyrroloindoline-containing na 近日，上海交大瞿旭东团队受邀在天然产物研究领域权威期刊Natural Product Reports发表题为《Biosynthesis of pyrroloindoline-containing natural products》的综述文章，针对吡咯并吲哚天然产物的生物合成途径中涉及的关键酶以及酶学机制进行了系统综述。生命科学技术学院博士后孙成海和博士生田文雅为本文共同第一作者，林芝助理研究员和瞿旭东教授为本文通讯作者。 吡咯并吲哚天然产物是一大类重要的天然产物，已知成员有数百种。不同的取代基、立体选择性和区域选择性，构成了此类天然产物骨架的多样性，从而也保障了这类化合物广泛的生物活性，如抗菌，抗肿瘤，抗疟原虫和抑制胆碱酯酶等。部分重要成员已被广泛地应用于临床，如治疗青光眼和胃动力障碍的physostigmine。鉴于这类天然产物独特的化学结构和巨大的药用潜力，备受有机合成和生物合成领域的瞩目。 上海交通大学生命科学技术学院瞿旭东教授课题组，长期致力于吡咯并吲哚生物碱生物合成及其关键酶的功能机制研究。前期解析了C3-芳香型吡咯并吲哚生物碱Naseseazine C的生物合成机制，发现了关键酶P450（NascB）催化吡咯并吲哚结构的形成 (Nat. Commun. 2018, 9, 4428); 近期，阐明了该类 P450 的催化机制以及对反应的立体和区域选择性的调控机制，通过对关键氨基酸的改造，实现了部分吡咯并吲哚分子骨架的精准合成(Nat. Commun. 2020, 11, 6251)；此外，发展了耻垢分枝杆菌（Mycolicibacterium smegmatis）全细胞催化体系，实现了该类分子骨架的高效生物合成（J. Org. Chem. 2021, 86, 11189）。 本文首先对吡咯并吲哚天然产物的重要性进行了介绍，并根据吡咯并吲哚C3位置取代基的不同将该类化合物分成了五类：type A (C3-无取代)，type B (C3-羟基取代)，type C (C3-烷基取代)，type D (C3-芳基取代) 和 type E (C3-吡咯并吲哚二聚)；随后，对每类中具有代表性的天然产物的发现和生物活性进行了简要介绍，对生物合成途径和涉及到的关键酶以及酶学机制进行了详细介绍；最后对该领域的未来进行了展望，得益于基因组挖掘和蛋白质工程的发展，更多样的吡咯并吲哚天然产物和后修饰酶将会被发现，同时结合酶工程改造，有助于高效合成多样的吡咯并吲哚类似物。 该工作得到国家自然科学基金（31770063和22107069），国家重点研发计划项目(2018YFA0900400)和上海市“超级博士后”激励计划(2019193)等科研项目的支持。