Introduction to Drug Discovery Research (ME:200.704) Spring 2018
Course Director: Takashi Tsukamoto (firstname.lastname@example.org)
Location: Rangos Building Room 590 Time: 10:00 AM – 11:30 AM Dates: Every Friday 1/12/2018-4/27/2018
This course provides an introduction to the various aspects of the drug discovery process including target identification, medicinal chemistry, in vitro and in vivo drug screening methods, pharmacokinetics, drug safety, intellectual property, and biologics. The last two lectures are devoted to case studies in which discovery of particular drugs will be discussed in detail to provide further insights into the process of drug discovery research. Each lecture is given by an expert on the given subject with many years of translational research experience. Students will gain a broad practical knowledge of drug discovery research that will allow them to prepare for a career in pharmaceutical research or basic medical science with implications for novel therapeutics. No prior knowledge in drug discovery is required. This course is recommended for students in the 2nd or subsequent years of their graduate program or medical school as well as postdoctoral fellows and faculty members interested in drug discovery research. Blackboard will be used to communicate with students, share course materials, make announcements, and post grades. Grades will be determined by quiz participation (given at the end of each lecture, 1/3), Mid-term Exam (1/3), and Final Exam (1/3). No quiz will be given at the first lecture.
1/12 Introduction (Takashi Tsukamoto) This introductory lecture provides a historical perspective and current status of drug discovery and development including opportunities and challenges facing the pharmaceutical industry. This first lecture also covers the outline and key learning objectives of the course.
1/19 Drug-like properties and druggable targets (Takashi Tsukamoto) The second lecture deals with two important concepts in target-based drug discovery research, drug-like molecular property and druggable targets. Several key parameters that determine drug-likeness of a chemical compound as well as druggability assessment of a therapeutic target will be discussed in depth.
1/26 in vitro Pharmacology I (Camilo Rojas) The first of the two lectures on in vitro pharmacology describes the important role played by in vitro assays in drug discovery research and examines the most common methods and techniques involved in target-based assays for drug screening including enzymatic and receptor assays.
2/2 in vitro Pharmacology II (Camilo Rojas) The second lecture on in vitro pharmacology covers cell-based phenotypic assays commonly performed in drug discovery research. The second part examines development of high throughput screening (HTS) assays and statistical parameters used in evaluation and validation of the HTS assays.
2/9 Pharmacokinetics I (Rana Rais) The first of the two lectures on pharmacokinetics introduces various in vitro assays routinely used in drug discovery research including cell permeability, drug efflux, drug metabolism, drug-drug interaction, and protein binding. The lecture also explains how these assays can facilitate the prediction of pharmacokinetics, “what the body does to the drug”, of a small molecule.
2/16 Pharmacokinetics II (Takashi Tsukamoto) The second lecture on pharmacokinetics examines methods to assess pharmacokinetics of drugs in experimental animals. The lecture teaches calculation of key pharmacokinetics parameters routinely used for the evaluation of drug absorption, distribution, and clearance.
2/23 Drug Safety (Adaline Smith) This lecture gives an overview of toxicology studies performed during drug discovery and provides some examples of toxicology assays used for the assessment of cardiovascular toxicity, genetic toxicity, and cytotoxicity as well as methods to assess in vivo tolerability/toxicity.
3/2 Midterm Exam
3/16 in vivo Pharmacology (Krystyna Wozniak) This lecture covers various topics related to animal disease models. The topics covered in this lecture include ethical considerations in animal experiments, limitations of animal models in predicting clinical efficacy, and various methods to recapitulate human diseases in animals. The second part covers examples of selected disease models.
3/23 Intellectual Property (Jeff Childers) This lecture provides an overview of the intellectual property system relevant to drug discovery research, mainly patents claiming new compositions of matter and/or new therapeutic methods. The second part goes over some landmark court cases and legislative acts that have had a substantial impact on the current intellectual property landscape in the pharmaceutical sector.
3/30 Lead Optimization (Takashi Tsukamoto) In this lecture, the concept of lead optimization is discussed in detail in connection with the topics covered in the prior lectures. The second part introduces various structural optimization strategies to improve pharmacological properties with the ultimate purpose of identifying clinical candidates.
4/6 Biologics (Roland Kolbeck) This lecture covers the principles of biologics-based medicines. The lecture highlights contrasts between small molecule drugs and biologics-based drugs in a number of areas including routes of administration, sites of action, target specificity, safety, and manufacturing process. The lecture also uses benralizumab as a case study to examine the process of biologics discovery and development.
4/13 Case Study I: Sitagliptin (Jim Barrow) The first of the two case study lectures goes over discovery and development of sitagliptin (JANUVIA®), the first dipeptidyl peptidase-4 (DPPIV) inhibitor approved by FDA for the treatment of type 2 diabetes. The lecture highlights a number of key elements that led to its successful development despite some initial challenges.
4/20 Case Study II: Imatinib (David Meyers) The second case study lecture examines discovery and development of imatinib (Gleevec®), the first kinase inhibitor approved by the FDA for the treatment of chronic myelogenous leukemia (CML). The lecture examines a series of key genetic oncology findings that led to the exploration of Bcr/Abl tyrosine kinase as a therapeutic target, leading to one of the most important target-based anticancer agents.
4/27 Final Exam
Important information for students with disabilities: All students with disabilities who require accommodations for this course should contact Catherine L. Will, Disability Services Coordinator for Graduate Biomedical Education (email@example.com or 410-614-3781) at their earliest convenience to discuss their specific needs. Please note that accommodations are not retroactive.