Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation

加速新药的发现和开发：促进国家健康的繁荣伙伴关系

• 批准号: EP/S035990/1
• 负责人: William Kerr
• 金额: $ 712.63万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS035990%2F1
• 关键词: Accelerated; Discovery; Development; New; Medicines

GSK is a global healthcare company that discovers, develops and manufactures medicines to treat a range of conditions including: respiratory diseases, cancer, heart disease, epilepsy, bacterial and viral infections (such as HIV and lupus), and skin conditions like psoriasis. GSK makes over 4 billion packs of medicines each year, with the goal of playing its part in meeting some of society's biggest healthcare challenges.Alongside a mission to provide transformative medicines to patients, GSK continually seeks to improve the efficiency and sustainability of our processes across the discovery, manufacturing, and delivery components of our supply chain. Indeed, GSK are committed to ambitious sustainability goals by 2050 that can only be achieved by making existing and future medicines via better routes, driving innovation all the way from the first design of the molecule through to patients in the clinic.This Prosperity Partnership aims to build on existing vibrant collaborations between GSK and the Universities of Nottingham and Strathclyde. The strengths of each partner will be leveraged to deliver a new suite of methods and approaches to tackle some of the major challenges in the discovery, development, and manufacture of medicines. Our vision is to increase efficiency in terms of atoms, energy, and time; resulting in transformative medicines at lower costs, reduced waste production, and shorter manufacturing routes. Key challenge areas, or themes, covered in our partnership include:1. The development and application of Artificial Intelligence (AI) and Machine Learning to the efficient identification of next generation medicines: in Drug Discovery, many hundreds of candidate structures are designed, prepared, and tested to find the molecule with the right profile to take into the clinic. The development of AI informed decision making has the potential to deliver huge savings by minimising the number of compounds that need to be made at this stage. The software developed will incorporate green chemistry principles with the goal that the chemical methods employed are as efficient and sustainable as possible.2. Next generation catalysis and synthesis: Chemists seeking to discover new medicines need new reactions that will allow them to make and investigate structures that are currently difficult, or even impossible, to make. A key objective of this proposal will be to develop new reagents, catalysts, and reactions to facilitate the more efficient preparation of drug-like molecules to accelerate drug discovery. Similarly, we will develop new ways of performing some of the most common chemical transformations in the synthesis of medicines whilst avoiding the use of carcinogenic reagents.3. Sustainable processes that deliver efficiency and transition to scale-up from grammes to kilogrammes. Currently under-utilised approaches, such as electrochemistry, will be explored for their ability to catalyse reactions with cheaper and less environmentally impactful metals, such as replacing palladium with nickel.4. A new Digital Design toolset for equipment will enable Digital Manufacturing of novel pharmaceutical processing equipment. Current development relies on existing traditional vessels and flow reactors that compromise our ability to deliver processes that operate at optimal performance. The research will couple advanced process models, state-of-the-art experimentation, and 3-D printing/additive manufacturing technologies to revolutionise how we develop, scale up, and operate chemical processes to supply new medicines. Integration of the projects and the expertise from the three partner institutions, and the successful prosecution of our research objectives, will make a major contribution to the wider pharmaceutical sector and, indeed, GSK's mission of discovering and developing transformative medicines faster to help people do more, feel better, and live longer.

葛兰素史克是一家全球性的医疗保健公司，致力于发现、开发和生产治疗一系列疾病的药物，包括：呼吸系统疾病、癌症、心脏病、癫痫、细菌和病毒感染（如艾滋病毒和狼疮）以及牛皮癣等皮肤病。GSK每年生产超过40亿包药品，其目标是在应对一些社会最大的医疗保健挑战方面发挥自己的作用。除了为患者提供变革性药物的使命外，GSK还不断寻求提高我们在供应链的发现、制造和交付环节的效率和可持续性。事实上，葛兰素史克致力于到2050年实现雄心勃勃的可持续发展目标，只有通过更好的途径生产现有和未来的药物，推动从分子最初设计到临床患者的全程创新，才能实现这一目标。这一繁荣伙伴关系旨在建立GSK与诺丁汉大学和斯特拉斯克莱德大学之间现有的充满活力的合作关系。将利用每个合作伙伴的优势，提供一套新的方法和途径，以应对药物发现、开发和生产中的一些重大挑战。我们的愿景是提高原子、能量和时间方面的效率；从而以更低的成本生产变革性药物，减少废物产生，缩短生产路线。我们的合作伙伴关系涵盖的主要挑战领域或主题包括：人工智能（AI）和机器学习的发展和应用，以有效识别下一代药物：在药物发现中，数百种候选结构被设计、制备和测试，以找到具有正确特征的分子，并将其带入临床。人工智能的发展为决策提供了信息，通过最大限度地减少现阶段需要制造的化合物数量，有可能带来巨大的节省。开发的软件将结合绿色化学原则，其目标是所采用的化学方法尽可能高效和可持续。下一代催化和合成：寻求发现新药物的化学家需要新的反应，这将使他们能够制造和研究目前难以制造，甚至不可能制造的结构。这项提议的一个关键目标是开发新的试剂、催化剂和反应，以促进更有效地制备类药物分子，从而加速药物的发现。同样，我们将开发新的方法，在药物合成中进行一些最常见的化学转化，同时避免使用致癌试剂。可持续的过程，提供效率和过渡规模，从克到公斤。目前未充分利用的方法，如电化学，将被探索其催化与更便宜和对环境影响较小的金属的反应的能力，例如用镍代替钯。一种新的设备数字化设计工具集将使新型药品加工设备的数字化制造成为可能。目前的发展依赖于现有的传统容器和流动反应器，这损害了我们提供最佳性能运行过程的能力。这项研究将结合先进的工艺模型、最先进的实验和3d打印/增材制造技术，彻底改变我们开发、扩大和操作化学工艺以供应新药的方式。三家合作机构的项目和专业知识的整合，以及我们研究目标的成功实施，将为更广泛的制药行业做出重大贡献，实际上，GSK的使命是更快地发现和开发变革性药物，帮助人们做得更多、感觉更好、活得更久。

项目成果

Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives.

• DOI: 10.1002/anie.202106352
• 发表时间: 2021-11-15
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Anderson, Joseph M.;Measom, Nicholas D.;Murphy, John A.;Poole, Darren L.
• 通讯作者: Poole, Darren L.

Organometallic Bridge Diversification of Bicyclo[1.1.1]pentanes

• DOI: 10.1002/chem.202304070
• 发表时间: 2024-01-10
• 期刊: CHEMISTRY-A EUROPEAN JOURNAL
• 影响因子: 4.3
• 作者: Anderson，Joseph M.;Poole，Darren L.;Measom，Nicholas D.
• 通讯作者: Measom，Nicholas D.

A sustainable and scalable multicomponent continuous flow process to access fused imidazoheterocycle pharmacophores

• DOI: 10.1039/d0gc03675g
• 发表时间: 2021-01-07
• 期刊: GREEN CHEMISTRY
• 影响因子: 9.8
• 作者: Baker, Blake J. M.;Kerr, William J.;Poole, Darren L.
• 通讯作者: Poole, Darren L.

Efficient Ligand Discovery Using Sulfur(VI) Fluoride Reactive Fragments.

• DOI: 10.1021/acschembio.3c00034
• 发表时间: 2023-09-15
• 期刊: ACS CHEMICAL BIOLOGY
• 影响因子: 4
• 作者: Aatkar, Arron;Vuorinen, Aini;Longfield, Oliver E.;Gilbert, Katharine;Peltier-Heap, Rachel;Wagner, Craig D.;Zappacosta, Francesca;Rittinger, Katrin;Chung, Chun-wa;House, David;Tomkinson, Nicholas C. O.;Bush, Jacob T.
• 通讯作者: Bush, Jacob T.

Efficient Ligand Discovery Using Sulfur(VI) Fluoride Reactive Fragments

使用六氟化硫反应片段高效发现配体

• DOI: 10.26434/chemrxiv-2022-6mt7k-v2
• 发表时间: 2022
• 作者: Aatkar A