Lecture No.

01

Course Leader: Dr. Parasuraman.P

[Link]@[Link]

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 Content

• Drug

• Drug discovery and development

• Modern methods of drug discovery

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Faculty of Pharmacy © Ramaiah University of Applied Sciences
 Lecture No. 01

• At the end of this lecture, student will be able to

– Describe the different stages of drug discovery process.

– Explain the various drug targets.

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 What is drug ??

• The term "drug" means [any] particles intended for use in the

diagnosis, cure, mitigation, treatment, or prevention of disease in

man or other animals

• A drug is any chemical or biological substance, synthetic or non-

synthetic

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 Sources of drugs
Animal insulin (pig, cow)
growth hormone (man) (Creutzfeldt-Jakob)
Plant digitalis (digitalis purpurea - foxglove)
morphine (papaver somniferum)
Inorganic arsenic mercury
lithium
Synthetic chemical (propranolol)
biological (penicillin)
biotechnology (human insulin)
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 Why are new drugs needed?

unmet medical need; new diseases (Swine flu; AIDS, Alzheimer’s; obesity);
low efficacy (dementia, cancer); side effects (antidepressants, antipsychotics)
downstream health costs; (Alzheimer’s; spinal injury)
cost of therapy; (Interleukins)
sustain industrial activity; pharmaceutical industry employs thousands and
makes a massive contribution to overseas earnings); patent expiry
Drug resistance:

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 History of Drug Discovery :

Pre 1919 1920s, 30s

• Herbal Drugs
• Serendiptious • Vitamins
discoveries • Vaccines

1940s
• Antibiotic Era
• R&D Boost due to
WW2

1950s 1960s
• New technology, • Breakthrough in
• Discovery of DNA Etiology

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 Complexity of Drug Discovery
1 Drug Molecule
Finding a Molecule that Satisfies Multiple
Criteria manufacturable
patentable
non-mutagenic
non-teratogenic
durable
reversible
non-inducing
metabolically stable
permeable
soluble
physically stable
potent
10,000 Drug selective
Candidates
targeted
Valid Biomedical
Hypothesis?
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 Drug Discovery & Development
Identify disease

Find a drug effective

against disease protein
Isolate protein (2-5 years)
involved in Scale-up
disease (2-5 years)

Preclinical testing Human clinical trials

(1-3 years) (2-10 years)

IN le
D
Fi

A
ND
Formulation

le
Fi
FDA approval
(2-3 years)
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 Modern drug discovery process
Target Target validationLead Lead Preclinical phase Drug
identification identification optimization discovery

6-9 years
2-5 years

• Drug discovery is an expensive process involving high R & D cost and

extensive clinical testing
• A typical development time is estimated to be 10-25 years.
•Costs an average of 1000 to 1500 million U.S. dollars per drug

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 DRUG Drug Discovery & Development-
DISCOVERY
Timeline

PRECLINICAL

CLINICAL TRIALS FDA

REVIEW
10,000 250 1 FDA
COMPOUNDS COMPOUNDS 5 COMPOUNDS APPROVE
D DRUG

~6.5 YEARS ~7 YEARS ~1.5 YEARS

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 Technology is impacting this process
GENOMICS, PROTEOMICS & BIOPHARM.
Potentially producing many more targets
and “personalized” targets

HIGH THROUGHPUT SCREENING

Identify disease Screening up to 100,000 compounds a
day for activity against a target protein
VIRTUAL SCREENING
Using a computer to
Isolate protein predict activity

COMBINATORIAL CHEMISTRY
Rapidly producing vast numbers Find drug
of compounds
MOLECULAR MODELING
Computer graphics & models help improve activity
Preclinical testing
IN VITRO & IN SILICO ADME MODELS
Tissue and computer models begin to replace animal testing
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 Drug discovery technologies
• Target identification
– Genomics, gene expression profiling and proteomics
• Target Validation
– Gene knock-out, inhibition assay
• Lead Identification
– High throughput screening, fragment based screening,
combinatorial libraries
• Lead Optimization
– Medicinal chemistry driven optimization, X-ray crystallography,
QSAR, ADME profiling (bioavailability)
• Pre Clinical Phase
– Pharmacodynamics (PD), Pharmacokinetics (PK), ADME, and
toxicity testing through animals
• Clinical Phase
– Human trials
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 Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studies Trials and
Therapeutics
• Cellular • Synthesis • Library • Drug • Animal
and and Developm Affinity models of
Genetic Isolation e-nt and Disease
Targets • Combinat • SAR Selectivity States
• Genomics or-ial Studies • Cell • Behaviour
• Proteomic Chemistry • In Silico Disease al Studies
s • Assay Screening Models • Functiona
• Bioinform developm • Chemical • MOA l Imaging
at-ics e-nt Synthesis • Lead • Ex-Vivo
• High- Candidate Studies
Throughp Refineme
ut nt
Screening

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 Summary

 Drug.
 Need for new drug.
 Different stages of discovery process.
 Drug discovery time.
 Cost of drug discovery.
 Technology impact on drug discovery.

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