Computer aided drug design (CADD) involves 5 steps: new lead discovery, lead optimization, preclinical lead development, clinical development, and post marketing surveillance. New lead discovery involves finding relevant enzymes/receptors through assays, purifying and characterizing them, determining structures, and screening known and designed compounds. Lead optimization develops secondary assays, tests related structures, and analyzes structure-activity relationships and properties. Preclinical development focuses on large scale synthesis, animal safety studies, and formulation experiments. Clinical development includes human safety studies and clinical trials. Post marketing surveillance collects usage and side effect reports. Strategies for new leads include isolating from nature, modifying natural products, screening known substances, and structure-based design.

1. DRUG DESIGNING

2. CADD
● Computer Aided/Assisted Drug Desig/Discovery
● Has 5 steps
– New lead Discovery
– Lead Optimization
– Preclinical Lead Develpment
– Clinical Development
– Post marketing Surveillance

3. New Lead Discovery
● Find a repeatable, High-capacity assay related to
the disease of intrest
● Continue to refine the assay
● Purify the biomaterials
● Get reproducable results
● Isolate relevent enzymes/receptors
● Purify, characterize and clone them
● Get their structural information
● Chose one or more standard compounds for assay
development/calibration

4. New Lead Discovery
● Screen known compounds randomly or in
pattern
● Design (hypothesis), synthesize and test new
compounds
● Use knowledge of related assays and structure
to form hypothesis
● Develop a idea for how actives may be working
mechanically

5. Lead Optimization
● Develop secondary assay to check specificity and
activity in animals
● Synthesize and test cogeneric structures
● Develop structure-activity or mechanism models
of action
● Calculate and measure physical properties
● Coorelate with activity
● Check safety in lower animals and cells

6. Preclinical lead development
● Develo[ large scale synthesis
● Animal safety studies on larger animals
● Drug delivery-elimination-metabolism studies
(ADME)
● Drug formulation experiments
● Dosage range study in animals

7. Clinical Development
● Prepare investigational new drug application
● Small scale safety and dosage ranging in healthy humans
● Develop clinical study protocol
● Obtain approval
● Recruit clinical investigators and patients for study
● Carry out the study
● Analuze and report results
● Present new drug application

8. Post marketing surveillance
● Collect usage and sude effect reports

9. Stratergy for new lead
● Isoloate from natural product – penicillin
● Modify the natural product – thienamycin
● Screen known synthetic substances – sulpha
drugs
● From structure-activity data – cephalosporin
● Structure-directed design – carbonic anhydrase
inhibitor
● Mechanism-based design – suicide inhibitors
● Chemist intution – enalapril

10. Stratergy for new lead
● Isoloate from natural product – penicillin
● Modify the natural product – thienamycin
● Screen known synthetic substances – sulpha
drugs
● From structure-activity data – cephalosporin
● Structure-directed design – carbonic anhydrase
inhibitor
● Mechanism-based design – suicide inhibitors
● Chemist intution – enalapril