TheDrugDiscoveryProcess(PPT).ppt

Drug Candidate safety testing Animal Studies - relevant species - transgenic KO/KI mice - conditional KOs - agonists/antagonists - antibodies - antisense - RNAi Studies ofDisease Mechanisms Human Studies Phases I,II, III Target -receptor; -ion channel; -transporter;-enzyme; - signalling molecule Lead Search -Develop assays (use of automation) -Chemical diversity -Highly iterative process Molecular Studies The Drug Discovery Process Lead optimization -selectivity -efficacy in animal models -tolerability: AEs mechanism- based or structure-based?-pharmacokinetics -highly iterative process Drug Approval and Registration Target selection validation Discovery Development Target Selection Validation Define the unmet medical need (disease) Understand the molecular mechanism of the disease Identify a therapeutic target in that pathway (e.g gene, key enzyme, receptor, ion-channel, nuclear receptor) Demonstrate that target is relevant to disease mechanism using genetics, animal models, lead compounds, antibodies, RNAi, etc. Discovery Develop an assay to evaluate activity of compounds on the target - in vitro (e.g. enzyme assay) - in vivo (animal model or pharmacodynamic assay) Identify a lead compound screen collection of compounds (“compound library”) compound from published literature screen Natural Products structure-based design (“rational drug design”) Optimize to give a “proof-of-concept” molecule—one that shows efficacy in an animal disease model Optimize to give drug-like properties—pharmacokinetics, metabolism, off-target activities Safety assessment, Preclinical Candidate!!! Development Pharmaceutical RD Formulation Clinical Investigator patient Clinical Pharmacology Clinical Research Statistics Epidemiology Data Coordination Research Information Systems Information Services Regulatory Affairs Project Planning Management Marketing Process RD Chem Eng. RD Manufacturing Bio Process RD Safety Assessment Toxicology Drug Metabolism (ADME) Pharmac