Week 1 Drug Discovery (DDD) PDF

LEARNING OBJECTIVES 1. Recognize, identify and discuss the importance of drugs 2. Discuss the development of pharmaceutical industry 3. Demonstrate knowledge on drug discovery and development overview, ethnopharmacology, natural product research and basic biology of disease ...

LEARNING OBJECTIVES 1. Recognize, identify and discuss the importance of drugs 2. Discuss the development of pharmaceutical industry 3. Demonstrate knowledge on drug discovery and development overview, ethnopharmacology, natural product research and basic biology of disease  DRUG DISCOVERY The process of drug discovery involves the identification of lead and its targets, synthesis, characterization, screening, and assays for therapeutic efficacy of lead. Once a compound has shown its value, it will begin the process of drug development prior to clinical trails  DRUG OVERVIEW “Drug" means: Articles recognized in the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and  DRUG OVERVIEW “Drug" means: Articles (other than food) intended to affect the structure or any function of the body of man or animals; and Articles intended for use as a component of any articles specified in clauses (1), (2), or (3), but not include devices or their components, parts, or accessories.  PHARMACEUTICAL CENTURY Patents & Potions PATENT a government authority or license conferring a right or title for a set period, especially the sole right to exclude others from making, using, or selling an invention. POTION a liquid with healing, magical, or poisonous properties  PRESENT: DRUG DISCOVERY Begins in the laboratory with scientists of various functional areas working together to identify cellular and genetic factors that play a role in specific disease PRE-DISCOVERY Understanding the disease Know the underlying cause for the disease Try to understand how genes are altered – how they affect proteins they encode How proteins interact with each other in living cells How those affected cells change the specific tissue they are in FINALLY, how the disease affect the entire patient The cinchona tree (left) and The common foxglove plant (Digitalis quinine (right) were important purpurea, left) contains cardiac players in the treatment of glycosides such as Digoxin (right), malaria infection for over 300 which are known to increase cardiac years. contractility via inhibition of myocardial sodium/potassium ATPase.  STEPS IN DRUG DISCOVERY  STEPS IN DRUG DISCOVERY 1. Target Selection 2. Target Identification 3. Target Prioritization/ Validation 4. Lead Identification 5. Lead Optimization  TARGET SELECTION defined as the decision to focus on finding an agent with a particular biological action that is anticipated to have therapeutic utility.  PROTEIN TARGET MOLECULE Naturally existing cellular Receptor or molecular structure Enzyme involved in the disease Transport molecule pathology on which the Ion channel drug acts. Tubulin Immunophilin  TARGET IDENTIFICATION Scientists use a variety Cellular and Genetic Targets of techniques to identify and isolate individual Genomics targets to learn more about their functions and Proteomics how they influence disease Bioinformatics CELLULAR & GENOMICS GENETIC TARGETS The study of genes and their function Involves identification of the target Exploit the findings from the receptors or enzymes whereas for sequencing of the human and some biologic approaches the other genomes to find new drug focus is at the gene or targets. transcription level. Based on 5 or 10 linked Drugs usually act on the targets, proteins per gene, proposes which are associated with disease. that the number of potential drug targets may lie between 5,000 or 10,000. PROTEOMICS BIOINFORMATICS “Proteome” It plays a key role in various It is also at the protein level stages of the drug discovery that disease processes process including: become manifest, and at which Target identification most (91%) drugs act. Computer screening of Target identification with chemical compounds proteomics is performed by Pharmacogenomics comparing the protein expression levels in normal and diseased tissues.  TARGET VALIDATION Involves demonstrating that a molecular target is critically involved in a disease process and modulation of the target is likely to have a therapeutic effect. Experimental approach by which a “potential” drug target can be tested and given further credibility.  LEAD IDENTIFICATION A lead compound or substance is one that is believed to have potential to treat disease. No intellectualization and RANDOM assays SCREENING Also known as  Investigation of a great NON-RANDOM targeted/focused/more number of compounds narrow approach for a particular problem or feature of them Whether the “hits” against the CROSS chosen target will interfere with other related targets.  CONFIRMED VALIDATED PRIMARY HIT HIT HIT  compound giving positive result in a  compound is  compound hit that screening assay confirmed as shows selective positive when activity assay is repeated A compound that HIT passes such a “screen”  LEAD OPTIMIZATION compares the properties of various lead compounds and provides information to help biopharmaceutical companies select the compound or compounds with the greatest potential to be developed into safe and effective medicines  The lead optimization cycle begins with the identification of a lead structure (“hit”) in a relevant biological assay. New analogs with structural modifications are prepared and screened in the biological assay.