Chem 162A/262A
Drug Design
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Chem 162A/262A |
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Dr. Kalju Kahn
Office: PSB-N 2623
Office hours: Tue 12:30-1:30 PM, and Thu 12:30-1:30 PM
Phone: 893-6157
E-mail: kalju@chem.ucsb.edu
Website: http://www.chem.ucsb.edu
Robert Levenson
Office: Chem 1317
Phone: 893-5468
E-mail: rlevenson@chem.ucsb.edu
To teach principles that govern the process of modern drug discovery and development. Students in the course follow a path similar to that taken by real-life drug developers by learning important elements of the drug design process in a logical order. Chem 162A, the first in the two-course series focuses on principles of rational drug design. Topics covered include target identification and validation technologies, generation and screening of chemical libraries for finding lead compounds, and modern medicinal chemistry approaches for ligand-based lead optimization. We will cover membrane-bound ion-channels and receptor proteins, and discuss strategies for finding agonists and antagonists for these types of targets.
The second course in the series, Chem 162B, will be taught in the Spring of 2009. The latter course focuses on structure-based drug design. It will outline experimental and computational methods for the study of ligand-protein complexes, and discuss how the knowledge of the three-dimensional structure of the active site helps in the lead optimization process. Chem 162B will also cover approaches used to design competitive and mechanism-based inhibitors based on the mechanistic understanding of enzyme catalysis. Finally, issues of pharmacokinetics and drug metabolism will be dealt with. Students are allowed to take Chem 162B/262B without taking Chem 162A/262B this academic year.
Lecture: MWF 12:00-12:50 Place: Phelps 1444
Computer Lab: Open day access Place: Chem 1153
| Syllabus | General information about the course. | |
| Textbook | The Organic Chemistry of Drug Design and Drug Action by Richard B. Silverman (Second Edition) | Amazon |
| Sample Lecture | Target Validation. (No Password Needed) Warning: Large File | PDF WAV |
| Last Years | Drug Design (by Dr. Kalju Kahn) website for Winter 2008 | Link |
| Last Years | Drug Design (by Dr. Kalju Kahn) website for Winter 2007 | Link |
| Last Years | Drug Design (by Dr. Kalju Kahn) website for Fall 2005 | Link |
| Last Years | Drug Design (by Dr. Kalju Kahn) website for Winter 2005 | Link |
| Last Years | Drug Design (by Dr. Kalju Kahn) website for Spring 2004 | Link |
| Last Years | Drug Design (by Dr. Norbert Reich) website for Spring 2003 | Link |
| Exam | Midterm Preparation Guide | |
| Exam | Final Preparation Guide | |
| Exam Sample I | Sample questions with answers from Spring 2004 | |
| Exam Key | Midetrm Exam Key (W 2009) | |
| Upload | Submit your assignments as PDF files | Link |
Course notes will be posted here before 7:30 a.m. of the lecture day. The lecture slides are password-protected. Contact your instructor to obtain the password.
| Notes | Lecture Notes. Powerpoint Pages in PDF | Acrobat |
| Jan 5 | Overview of the course. History of Drug Design. | |
| Jan 9 | Rational Drug Design: Overview of Approaches | |
| Jan 12 | Diseases and the Biological Concept | |
| Jan 14 | Target Validation: Principles | |
| Jan 16 | Target Validation: Pre-Genomic Methods | |
| Jan 21 | Target Validation: Post-Genomic Methods | |
| Jan 23 | Target Validation Tutorial | Link |
| Jan 28 | Enzymes as Drug Targets | |
| Feb 2 | Receptors as Drug Targets: Ion Channels | |
| Feb 4 | Receptors as Drug Targets: Ion Channels | |
| Feb 4-6 | Receptors as Drug Targets: GPCRs | |
| Feb 11 | Study of Membrane Receptors | |
| Feb 13 | Assays | |
| Feb 18 | Combinatorial Chemistry | |
| Feb 20 | Ligand-based drug design and optimization | |
| Feb 23-25 | Ligand-based drug design and optimization | |
| March 2 | Fragment-based drug design and optimization | |
| March 4 | QSAR | |
| March 9 | Nucleic Acid Drugs |
| Literature | Required reading in PDF | Acrobat |
| General | From Serendipity to Rational Drug Design | |
| History | Drug Discovery: A Historical Perspective | |
| Future | Drug Research: Myths, Hype and Reality | |
| General | Antibacterial discover strategy: GSK story | |
| Targets | Potential New Drug Targets for Osteoporosis (Deal, 2009) | |
| Receptors | Principles: Receptor Theory in Pharmacology (Kenakin, 2004) | |
| Receptors | Epibatidine: Impact on Nicotinic Receptor Research (Dukat & Glennon, 2003) | |
| Receptors | How Antidepressants Block Neurotransmitter Reuptake | |
| Ligand-Based | Chemistry of 1,4-benzodiazepines (Sternbach, 1971) | |
| Ligand-Based | Molecular Superposition (Miller, 1998) | |
| Ligand-Based | Fragment-Based Drug Discovery (Erlanson, 2004) |
Suggested literature can be found now on a separate page
The assignments are posted one week before the due date. Answers shall be submitted electronically no later than the midnight of the due date.
| Assignments | PDF files | Acrobat |
| 1 | Molecular Mechanisms of Diseases. General Principles of Drug Design | |
| 2 | Target Validation: Due Jan 30 | |
| 3 | Receptors: general features and ligand design: Due Feb 6 | |
| 4 | Assays and CombiChem: Due Feb 25 | |
| 5 | Ligand-Based Drug Design: Conformation of Neuraminidase Inhibitors | Link |
| 6 | Ligand-Based Drug Design: Descriptors in QSAR | Link |
| 6 | Ligand-Based Drug Design: Statistics in QSAR | Link |
| 6 | QSAR Example 1: Antibacterial Activity of Sulfonamides | |
| 6 | QSAR Example 2: Anesthetic Activity of Barbiturates | |
| 6 | QSAR Example 3: Multiple Linear Regression: Capsaicin | NB |
The assignment keys are typically posted one week after the due date.
| Keys | PDF files | Acrobat |
| 1 | Molecular Mechanisms of Diseases. General Principles of Drug Design | |
| 2-A | Statistical Analysis of Microarray Data | |
| 2-B | Target Validation | |
| 3 | Receptors: general features and ligand design | |
| 4 | Assays and CombiChem | |
| 5 | Ligand-Based Drug Design: Conformation of Neuraminidase Inhibitors |
The project milestone guides are typically posted week and a half before they are due.
| Project Tips | General Guidelines to Project Development | |
| 1 | Disease Selection and Characterization | |
| 2 | Target Validation | |
| 3 | Identification of lead compounds, lead optimization |
Students in this course encounter many terms which have specific meaning in the context of drug design and medicine. You may find our glossary helpful when reading some of the assigned papers. If you encounter a term that is not in this dictionary, you could try a specialized medicinal chemistry glossary at www.chem.qmw.ac.uk/iupac/medchem ,an on-line dictionary at www.dictionary.com or an on-line encyclopedia at www.wikipedia.com . Feel free to send any additions and suggestions to Kalju Kahn
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Modern Drug Discovery
Nature Reviews Drug Discovery
Drug Discovery and Development
Drug Design Lecture Notes by Dr. Hugo Kubinyi
Oxford Drug Resistance Group Lectures
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Acetylcholine Receptor
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Dr. Andrew Boa lecture notes
An Overview of Marine Drug Discovery
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