果冻影院

This modules explores the first half of the pipeline of drug discovery and development. It takes students through the process of deciding on a therapeutic concept (i.e. which disease should we try and treat) through the identification and/or discovery and/or design of pharmacologically active lead compounds or biological molecules that we hope will become successful drugs. This module is core to the MSc Drug Discovery programmes and is followed by its sister module "The Process of Drug Development" (TPODD2) in term 2. The module firstly covers an introduction to the molecular basis of disease, with examples of infection, genetic and multifactorial clinical conditions and the mechanism of action of certain drugs in their therapy. There is a detailed revision of basic macromolecular structure and the types of cellular components that constitute drug targets. We also examine the identification of drug targets and the genomic approaches to the validation of drug targets. Secondly we will consider lead compounds for drug discovery, defining what lead compounds are and examining the various sources of lead compounds that include natural products, chemical synthesis of compound libraries and high throughput screening of libraries. We will also introduce some topics covered in more detail elsewhere, including physiochemical properties, pharmacophores, rational drug design, QSAR, structure-based drug design, biopharmaceuticals and biosimilars. Key themes in the application of modern synthetic methods to medicinal chemistry and drug discovery are also covered. Chemical-synthetic techniques that are utilized in the preparation of compounds will be discussed; importance will be given to the generation of novel natural product-like or -derived compound libraries. Topics include combinatorial chemistry, solid phase and microwave chemistry, and chemistry in flow. Fragment based drug discovery will be explored in detail. We will also look in detail at molecular modelling and structure-based design, with a view to introducing the student to the principles and practice of modern drug discovery. The course will provide an awareness of rational drug design, based on understanding the three-dimensional structures and physicochemical properties of drugs and receptors. There is considerable 鈥渉ands on鈥� experience of molecualr graphics and computer-aided drug discovery. This section will cover modelling drug/receptor interactions with the emphasis on molecular mechanisms, molecular dynamics simulations and homology

modelling. Other topics will be selected from: conformational sampling, macromolecular folding, structural bioinformatics, receptor-based and ligand-based design and docking methods, in silico screening of libraries, semi-empirical and ab-initio methods, QSAR methods, molecular diversity, design of combinatorial libraries of drug-like molecules, macromolecular and chemical databases. Throughout the module, case studies in different areas of drug discovery are provided by lecturers to exemplify the different techniques covered. Topics include peripheral nerve repair, CNS drugs, antimicrobials, covalent irreversible inhibitors, and drug discovery for epigenetics and COVID-19. Finally, the module includes a mini research project in which students will conduct a series of lab-based experiments to gain experience in areas such as natural product extraction, compound synthesis and biological assays.

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