1. Today’s Drug Discovery Process “How Do We Discover Drugs” Dr. Vincent P. Gullo Drew University

2. Topics My background Research interests Drug discovery process Previous seminar topics Possible seminar topics

3. Background B.S. in Chemistry – City College of NY Ph.D. in Organic Chemistry – Columbia University Career in Drug Discovery –Spent 8 years at Merck focusing on discovering new drugs for cardiovascular disease, antibiotics and animal health drugs from natural sources –20 years at Schering-Plough working on discovering drugs from natural and synthetic compound sources for a broad range of therapeutic areas –3 years at a small biotech company searching for drugs from natural sources for a broad range of therapeutic areas.

4. Research Interests Antibacterials –Need to treat resistant microorganisms MRSA Carbapenem resistant enterobacteriaceae (CRE) –Lack of major interest by large pharma companies until recently –Can be done at Drew with undergraduates Microbiological assays (Demain) Synthetic chemistry and instrumentation available If we are successful, contacts with small company to follow up further

5. The Drug Discovery Process Target Selection Target Validation Assay Development Screening Hits & Leads Lead Optimization Development Clinical Trials Phase I, Phase II, Phase III New Drug Application Market & Phase IV & Timeline – 12 to15 years Cost – $1 to 1.6 billion

6. Search for a New Antibacterial Target selection and validation Inhibit growth of the bacteria - Numerous successes using this approach Microbial assay - agar diffusion assay

7. Screening and Hit/Lead Identification Test (screen) 250 compounds from Dr. Houlihan’s library of compounds prepared for anorexia and cocaine addiction 13 compounds discovered with similar structures Synthesizing analogs to improve potency, spectrum of activity and PK

8. Previous Research Topics The Antibiotic Crisis (What is the problem and how to address it) Drug Discovery Compound Sources: Natural or Synthetic Compounds Tuberculosis (difficulties in treating TB and what are potential solutions) Hepatitis C virus (Will we ever be able to have a complete viral response) Collateral Damage: Comparing Targeted Therapies to Non-Specific Chemotherapy in Cancer Induced Pleuripotent Stem cells and the Potential to Cure Type one Diabetes Cystic Fibrosis: Are We on the Pathway to a Cure How is Exploring Nature Helping Us to Fight Cancer? The Problem of Antibiotic Resistance and an Approach to Longer Lasting Treatments Future Prospects of Antifungal Therapies

9. Possible Research Reports Anything along the drug discovery pathway –Types of assays Phenotypic vs. Targeted –Natural products Role in today’s drug discovery process? –Diseases with unmet medical need Diabetes Heart disease Cancer Antibacterials/antifungals/antivirals