Drugs and design a drug

1. A short
Introduction to
Drug design and
discovery
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2. What is a drug?
• Defined composition with a pharmacological effect
• Regulated by the Food and Drug Administration (FDA)
• What is the process of Drug Discovery and Development?
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3. Drug designing
1)challenging
2)Expensive
3)Time consuming
So, Multidisciplinary approach:
Computational tools, methodologies for structure guided
approach + Global gene expression data analysis by
softwares.
Hence,
1)Efficiency increased
2)Cost effectiveness
3)Time saved
4)Strategies to overcome toxic side effects
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4. Drug design
Hence,
1)Efficiency increased
2)Cost effectiveness
3)Time saved
4)Strategies to overcome toxic side effects
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5. DRUG DESIGN
2 ways:
A)Development of ligands with desired properties
for targets having known structure and functions.
B)Development of ligands with predefined
properties for targets whose structural
information may be or may not be known.
This, unknown target information can be found by
global gene expression data.
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6. w drugs are taken?
 Inhaled
 Injection
 Orally
 Snorted
 Transdermal (Patches)
 Through body orifices
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7. A Little History of Computer
Aided Drug Design
• 1960’s - Viz - review the target - drug interaction
• 1980’s- Automation - high trhoughput target/drug selection
• 1980’s- Databases (information technology) - combinatorial
libraries
• 1980’s- Fast computers - docking
• 1990’s- Fast computers - genome assembly - genomic based
target selection
• 2000’s- Vast information handling - pharmacogenomics
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8. Drug Designing Methods:
• Databases:
PDB: Experimentally determined structures.
NCI: National Cancer Institute.
Pubchem: Bulk data available for QSAR for lead discovery.
3D MIND: Information about cytotoxic potency for 60 human cancer
cell lines.
OSIRIS: To draw chemical structures and predict drug like properties
like absorption in body etc.
Links at the bottom of the paper.
Autodock and Dock6 for docking
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9. Toxicity
• Toxicology is the study of toxic effects of drugs or
other substances on the body
• Physicians must weigh therapeutic benefit against the
risk of toxicity
• Some drugs have a narrow therapeutic-toxic index
called the “therapeutic window”
• very little difference exists in the therapeutic versus toxic
blood level
• laboratory drug levels are ordered if the physician suspects
toxicity
• Toxicity of a drug may affect route of administration
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10. Discovery and Development
• The time from conception to approval of a new drug is
typically 10-15 years
• The vast majority of molecules fail along the way
• The estimated cost to bring to market a successful drug is now
$800 million!! (Dimasi, 2000)
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11. Drugs and the Discovery
Process• Small Molecules
• Natural products
• fermentation broths
• plant extracts
• animal fluids (e.g., snake venoms)
• Synthetic Medicinal Chemicals
• Project medicinal chemistry derived
• Combinatorial chemistry derived
• Biologicals
• Natural products (isolation)
• Recombinant products
• Chimeric or novel recombinant products
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12. BASICCONCEPT OFTHE
DRUGMANAGEMENTCYCLE
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Management Support
Procurement
Planning
Distribution
Utilization
Storage

13. Advantages
 Patients receive optimal pharmaceutical therapy
 Enables consistent and predictable treatment from all
levels of providers and at all locations
 Allows for improved availability of medicines because
of consistent and known usage patterns
 Helps provide good outcomes because patients are
receiving the best treatment regimen available
 Lowers cost
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14. Disadvantages
 Inaccurate guidelines will provide the wrong information. Often
guidelines are based on existing practices rather than
evidenced-based medicine.
 Guideline development and maintenance takes much time and
effort.
 STGs may give false sense of security and discourage ongoing
critical thinking
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15. The biological targets of drug action
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16. • Medicine – a legal substance used to treat an illness or
ailment
• Side effects – an effect that accompanies the expected
effect of a drug
• Drug allergies – an unwanted effect that accompanies
the desired effect of a drug
• Overdose – a serious sometimes fatal reaction to a
large dose of a drug
• Dose – an exact amount of a drug
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17. Issues in Drug Discovery
• Hits and Leads - Is it a “Druggable” target?
• Resistance
• Pharmacodynamics
• Delivery - oral and otherwise
• Metabolism
• Solubility, toxicity
• Patentability
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18. Drug Discovery Without a Lead
Penicillins
1928 - Fleming
• mold spore contaminates culture dish
• left dish on bench top while on vacation
• weather was unseasonably cold
• particular strain of mold was a good penicillin producer
Bacteria lysed by green mold; could not reproduce effect -
serendipity.
Could not get penicillin in a useful clinical form
1940 - Florey (Oxford)
Succeeded in producing penicillin in a useful clinical form.
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19. Conclusion
• Cancer is common in all the ages and it shows metastasis,
angiogenesis and cell death, etc.
• So, drugs to cure cancer are necessary.
• Except toxicity, drugs are quite tolerable so they are combined
with other drugs.
• Comparative analysis of gene expression levels between drug
treated and non-treated condition should be studied.
• If getting superior quality drug than the available ones, clinical
trial phases can be performed on them.
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