BCMP 236. Modern Drug discovery: from principles to patients Tim Mitchison and Nathanael Gray (Medical School) and members of the Department Half course (spring term). Tu., Th., 3:30-‐5. This course will familiarize students with central concepts in drug action and therapeutics at the level of molecules, cells, tissues and patients. These concepts and methods are central to modern drug development and regulatory evaluation. In the course we will cover drug-‐target interactions, Pharmacokinetics and Pharmacodynamics at a quantitative level, the clinical trials process, biomarkers and new frontiers in Therapeutic development. This course will focus on modern approaches to therapeutic discovery and development, for small molecules, protein based therapeutics, nucleic acid based drugs, antibacterial compounds and nano particles. This course will follow the current paradigms and pipeline doe drug development from target identification to first in human studies. Examples are drawn from numerous unmet medical needs including cancer, HIV, neurodegenerative and infectious diseases. The course will include computational and quantitative exercises. Note: This course is a reworking of the BCMP 309qc and 307qc quarter courses. Spring 2014 Meeting Dates: January 29, February 3, 5, 10, 12, 17, 19, 24, 26, M arch 3, 5, 10, 12, 24, 26, 31 April 2, 7, 9, 14, 16, 21, 23, 28, 30, M ay 5,7,12 Meeting Time: 3h30pm to 5pm First Meeting: 1/29/2015 Final Meeting: 5/12/2015 Location: TMEC 126 Class size: May be limited Course Directors: Tim Mitchison: [email protected] ; Nathanael Gray: [email protected] TAs: Nieneke Moret and Adam Brown Course faculty: Catherine Dubreuil, [email protected] COURSE INFORMATION: (1) Detailed course goals and objectives: • Understand and analyze drug response pathways • Understand and analyze drug development pipelines • Know modern drug design paradigms • Quantitative analysis of Pharmacokinetics • Drug-‐receptor interactions • Understand differences in development, including PK, of small molecules, biologics, anti-‐bacterial agents. (2) Course outline: This course will have four main modules: 1. Module 1: Target Selection 2. Module 2: Target to hit (include small molecules, Biologics, nucleic acids and anti-‐-‐-‐bacterial) 3. Module 3: Preclinical drug development 4. Module 4: First in human (phase I and II trials) (3) Workload and assessments This course will have 2 separate types of assessments: in class discussions/presentations and problem sets. There will be a total of 5 quantitative problems sets. Students are NOT required to use MATLAB to do these and may use any software they choose if applicable. Each student must hand individual work. All Problem set will be due BEFORE the start of class on the due day. You must hand in your own individual assignments. Working with others on your is permitted, HOWEVER, YOU MUST NOTE WHO YOU WORKED WITH AND YOUR ANSWERS MUST BE YOUR OWN! Late papers will be accepted with a legitimate excuse, but may not get full credit. (4) Course policy and Student expectations Students are expected to come to lecture having read the materials in advance. Attendance to every discussion section is mandatory. Failure to attend tutorial due to an unexcused absence will severely impact the overall course grade. • Only excused absences will be considered: an example of an excused absence is a medical emergency and must be accompanied by a doctor's note OR other situations that will be determined by the course instructors. If you know you will not be able to attend a tutorial session, you must notify the course director in advance OR within 24 hours following the end of missed class. •
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Classroom Courtesy: As a courtesy to all the members of our classroom community, please turn off your cell phones and keep your side conversations to a strict minimum. • Students are expected to be punctual and arrive on time to lecture. Lectures will start on time •
Academic Honesty: You are expected to be familiar with and to follow the University’s policies on academic integrity and plagiarism: http://webdocs.registrar.fas.harvard.edu/ugrad_handbook/2009_2010/cha pter2/academic_dishonesty.html and http://isites.harvard.edu/icb/icb.do?keyword=k70847&pageid=icb.page355 322 All references and sources used in your assignments MUST be properly cited in accordance with Harvard guidelines. Instances of academic dishonesty may result in sanctions including but not limited to, failing grades being issued, and other consequences. BCMP 236 Schedule 2015
Date/time
Location
Lecturer
Topic
Modules: 01/29/2015: 3-‐5pm
TMEC 126
Tim Mitchison
Intoduction to the class, current drugs, difficult targets
Module 1: Kinetics, target and binding
Psets
02/03/2015: 3-‐5pm
TMEC 126
Tim Mitchison
Receptor theory, enzyme inhibition
Module 1: Kinetics, target and binding
02/05/2015: 3-‐5pm
TMEC 126
Discussion sections
Receptor theory, enzyme inhibition discussion
Module 1: Kinetics, target and binding
02/10/2015: 3-‐5pm TMEC 126
Steve Haggarty
Target selection Module 1: Target selection
02/12/2015: 3-‐5pm
TMEC 126
Steve Haggarty
Target selection cont. 45 mins
Discussion: Schizophrenia paper/targets 45 mins IN CLASS
Module 1: Target selection
02/17/2015: 3-‐5pm
TMEC 126
Steve Haggarty
Assay development for drug discovery
Module 2: Target to Hit
02/19/2015: 3-‐5pm
TMEC 126
Sara Buhrlage
Small Molecules 2: Screening and structure based design
Module 2: Target to Hit
Small molcules
02/24/2015: 3-‐5pm
TMEC 126
Sara Buhrlage
Small Molecules 3: Optimization, what makes a good molecule
Module 2: Target to Hit
Small molcules
02/26/2015: 3-‐5pm
TMEC 126
Tim Springer
Biologics 1: Therapeutics Antibody development
Module 2: Target to Hit
Biologics
03/03/2015: 3-‐5pm
TMEC 126
Tim Springer
Biologics 2: Protein Therapeutic development
Module 2: Target to Hit
Biologics
03/05/2015: 3-‐5pm
TMEC 126
Dinah Sah
Nucleic acid 1: siRNA
Module 2: Target to Hit
Nucleic acid
03/10/2015: 3-‐5pm
TMEC 126
Discusion sections
Nucleic acid 3: paper discussion or case study?
AAV gene therapy for ALS-‐SOD1 Module using 2: TRarget NAi to Hit
Nucleic acid
03/12/2015: 3-‐5pm
TMEC 126
Tim Mitchison
Pharmacodymanics
Module 3: Preclinical
03/24/2015: 3-‐5pm
TMEC 126
Tim Mitchison
Pharmacokinetics 1
Module 3: Preclinical
03/26/2015: 3-‐5pm
TMEC 126
Tim Mitchison
Pharmacokinetics 2
Module 3: Preclinical
03/31/2015: 3-‐5pm
TMEC 126
Natalie Agar
Pharmacokinetics 3
Module 3: Preclinical
04/02/2015: 3-‐5pm
TMEC 126
Suzanne Walker
Anti-‐bacterials 1: Antibiotic development, PK, TOX, Clinic
Module 2: Target to Hit
Anti bacterials
04/07/2015: 3-‐5pm
TMEC 126
Suzanne Walker
Anti-‐bacterials 2: Antibiotics, target selection and resistance
Module 2: Target to Hit
Anti bacterials
04/09/2015: 3-‐5pm
TMEC 126
Suzanne Walker or discussion?
Anti-‐bacterials 3: Anti virals or discussion? Compare contract AB with viral?
Module 2: Target to Hit
Anti bacterials
04/14/2015: 3-‐5pm
TMEC 126
Ofer Levy
Vaccine development
Module 2: Target to Hit
Vaccines
04/16/2015: 3-‐5pm
TMEC 126
Omid Farokhzad
Pharmacokinetics 4: Nano particles
04/21/2015: 3-‐5pm
TMEC 126
Omid Farokhzad
Pharmacokinects 5: Nano particles
04/23/2015: 3-‐5pm
TMEC 126
Vishal Vaidya
Toxicology
Module 3: Preclinical
04/28/2015: 3-‐5pm TMEC 126
Vishal Vaidya
Advanced topics in biomarkers
Module 3: Preclinical
04/30/2015: 3-‐5pm
TMEC 126
Natalie Agar
Imaging Biomarkers
Module 3: Preclinical
05/05/2015: 3-‐5pm TMEC 126
Discussion section
Discussion section
Phase 1 and 2 trials
05/07/2015: 3-‐5pm
TMEC 126
Tim Mitchison Failure, endpoints
Phase 1 and 2 trials
05/12/2015: 3-‐5pm
TMEC 126
Jerry Avorn
Trial design Jerry Avorn Regulatory Science
Phase 1 and 2 trials
Pset 1
Pset 2: Target selection
and assays
Pset 3: small molecules
Biologics
Nucleic acid Anti-‐bacterials
Pset 4: Quantitative PK
Module 3: Preclinical
discussion?
Module 3: Preclinical
Pset 5: Biomarker, Tox
first in man