This presentation will help you to know how to lead develop and drug discovery.

1. WELCOME
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2. Lead Development And Drug Discovery
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Presentation
on

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Content :
• Lead compound
• Lead identification
• Criteria for leads
• Sources of leads
• Drug discovery
• Drug development
• Phase of drug discovery
• Advantage

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• Chemical compound that has pharmacological or
biological activity likely to be therapeutically useful.
Lead compound :

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• Organic compounds are identified which interact
with target protein and modulate it’s activity by
using random or rational approaches.
Lead identification :

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• Pharmacological properties : Efficacy, Potency, Selectivity .
• Physiochemical properties : Water solubility, Chemical
stability .
• Pharmacokinetic properties : Metabolic stability and
toxological aspects .
• Check optimization potential : Ease of chemical synthesis
and derivatization.
• Potentiality
Criteria for leads:

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• Streptomyces notatum : Penicillin
• Streptomyces venezuelae : Chloramphenicol
• Penicillin griseofulvum : Griseofulvin
• Streptomyces griseous : Streptomycin
• Streptomyces gradiae: Neomycin
Sources of leads
Microorganisms :

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• Marine invertebrates : Arabinose
• Cone snail toxin : Ziconotide
• Dinoflagellates : Sax toxin
Sources of leads
Animal:

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• Papaver somniferum : Morphine
• Digitalis lanata : Digoxin
• Atropa belladonna : Atropine
• Cinchona trees : Quinine
Sources of leads
Plant :

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• Candidate molecules are chosen on the basis of their
pharmacological properties .
Drug discovery :

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• Preclinical development : Non human studies
( toxicity testing, pharmacokinetic analysis and
formulation areperformed)
• Clinical development : The selected compound is tested
efficacy, side effects and potential danger in volunteer and
patient.
Drug development :

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• Usual time duration : 2.5 years
• Usual no of projects: 100
• It consist of the following components
• Target selection and validation
• Lead finding or lead generation
• Lead optimization
• Pharmacological profiling
Drug discovery :

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• Phase 0
• Phase I
• Phase Ii
• Phase III
• Phase IV
Phases of drug discovery :

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• Study of new drug in micro dose to drive PK information
in human before undertaking phase I studies is known as
phase 0.
• Micro dose: Less than 1/100 of the dose of a test
substance calculated to produce pharmacological effect
with a maximum dose < 100.
• Objective : To obtain preliminary pharmaceutical data
• Preliminary data : Sub acute toxicity study in one species
by two routes of administration.
Phase 0 :

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• Clinical pharmacological Evaluation
• First stage of testing in human subjects.
• 20-50 Healthy volunteers
• Concerned with : o -Human toxicity and tolerated
dosage range.
o -Pharmacokinetics
o -Pharmacodynamics
o -Pharmacodynamics
Phase I :

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• SAD ( Single Ascending Dose)
• MAD ( Multiple Ascending Dose)
• Food effect
Types of phase I Trails

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• Controlled clinical Evaluation
• 50-300 patients
• Concerned with o -Safety
o -Efficacy
o -Drug toxicity
o -Drug toxicity
Phase II :

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• Phase IIA: Designed to assess dosing requirements.
• Early phase
• Pilot clinical trails
• 20-200 patients
• Not multiple centric
• Single Blind comparison with a standing drug.
• Phase IIB: Designed to study efficacy.
• Late phase
• Pivorate clinical trails
• 50-300 patients
• Multi centric
• Double Blind compared with a placebo or standing drug.
Drug interaction
Phase II types:

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• Extended clinical trails
• Most expensive and time consuming
• 250-1000 patients
• Controlled Double Blind Technique
• Concerned with o -Safety, Efficacy
o -Comparison with other drugs
o -Package insert
o -Package insert
Drug interaction
Phase III:

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• Post marketing surveillance
• Designed to detect any rare or long term adverse effects.
• Adverse drug reaction monitoring
• Pharmacovigilance.
Drug interaction
Phase IV :

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• Tax incentives
• Enhanced patent protection and marketing rights.
• Clinical research financial
• Rise in research and development
• Crown corporation
Advantage :