1. Drug Discovery Primary objective－
design & discovery of new compounds that are suitable for use as drugs
A team of workers－ chemistry, biology, biochemistry, pharmacology, mathematics, medicine & computing …
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2. Administration method Development of tests
Requirements
Synthesis of the drug
Administration method
Development of tests
Procedures to establish how it operates
in the body
(v) safety assessment
research into the biological and chemical nature of diseased state.
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3. Potency: quantitative nature of the effect
Drugs: Definition
Chemical substances that are used to prevent or cure diseases in humans, animals and plants
Activity: Pharmaceutical/pharmacological effect on the subject, e.g. Analgesic or β-blocker
Potency: quantitative nature of the effect
An analgesic, or painkiller, is any member of the group of drugs used to achieve analgesia — relief from pain. The word analgesic derives from Greek ἀν-, "without", and ἄλγος, "pain".[1]
used for the management of cardiac arrhythmias, protecting the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention),[1] and, in certain cases,hypertension.[2][

4. Drugs Properties: ADMET
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5. Areas Influencing DD Molecular Biology on Drug Discovery
High-Throughput Screening
Combinatorial Chemistry
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6. Molecular Biology Influence
Genetic information
Biochemical and chemical terms.
Cloning and expressing genes that encode therapeutically useful protein
Having or exhibiting healing powers: a therapeutic agent; therapeutic exercises.
 Of or relating to the medical treatment of a disease or condition.

7. High Throughput Screening
Widely used in the pharmaceutical industry.
Automation to quickly assay the biological or biochemical activity of a large number of drug-like compounds.

9. Combinatorial Chemistry
Laboratory technique in which millions of
molecular constructions can be synthesized and tested for biological activity.

10. Even the drugs abused have their activity. No drug is completely safe.
Drug: agent used for the psychotic effect by the media or general public.
Even the drugs abused have their activity.
No drug is completely safe.
Suitable quantity to cure or excess to be poisonous! e.g. aspirin, paracetamol
can be toxic if excesses.
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11. Pharmacogenetics It is the branch of pharmacology concerned
with the effect of genetic factors on reactions to drugs.
how people respond to medicines
Correlating heritable genetic variation to drug response
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12. Pharmacogenetics Biotechnological science combines techniques of
medicine
pharmacology
(iii) genomics
developing drug therapies to compensate for genetic differences in patients which cause varied responses to a single therapeutic regimen.
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13. Change Management

14. Pharmacogenomics How genes affect persons response to drugs.
Pharmacology (science of drugs)
Genomics (the study of genes and their functions)
Develop effective, safe medications & doses
tailored to a person’s genetic makeup.
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15. Change Management

16. Single Nucleotide Polymorphisms
Most common type of genetic variation among people.
Each SNP represents a difference in a single
DNA building block, i.e. nucleotide.

17. Single Nucleotide Polymorphism
AAGCCTA
AAGCTTA
contain a difference in a single nucleotide.

19. In reality few SNPs act on their own
Genome-Wide Association Studies identify groups of SNPs linked to a certain condition
Non-coding regions of DNA
When frequent enough in a population they can be linked to specific traits, e.g. a disease
SNP microarrays can be used to probe hundreds of thousands of SNPs in
parallel

20. Methods of DD
Past:
(i) Identification of active ingredient from traditional remedies
(2) serendipitous discovery.
Current:
Diseases are controlled at molecular & physiological level.
Information of Human Genome
Physiology (/ˌfɪziˈɒlədʒi/; from Ancient Greek φύσις (physis), meaning "nature, origin", and -λογία (-logia), meaning "study of"[1]) is the scientific study of normal function in living systems.[2] A sub-discipline of biology, its focus is in how organisms, organ systems,organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system.[3] Given the size of the field it is divided into, among others, animal physiology (including that of human), plant physiology, cellular physiology

21. Drug Discovery - Methods
Pre 1919
Herbal Drugs
Serendiptious discoveries
1920s, 30s
Vitamins
Vaccines
1940s
Antibiotic Era
R&D Boost due to WW2
1950s
New technology,
Discovery of DNA
1960s
Breakthrough in Etiology
1970s
Rise of Biotechnology
Use of IT
1980s
Commercialization of Drug Discovery
Combinatorial Chemistry
1990s
Robotics
Automation
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22. Drug Discovery - Methods
Random Screening
Molecular Manipulation
Molecular Designing
Drug Metabolites
Serendipity
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23. Drug Discovery – Pipeline
Target Identification
Target Validation
Lead Identification
Lead Optimization
Pre-Clinical Pharmacology & Toxicology

24. Drug Discovery Animal Studies Clinical Tests Commercialization
Gene or Genome
Sequencing
Target
Validation
Discovery
Lead
Pre-
Clinical
Manufac
-turing
Phase I
Phase II
Phase III
Distribution
Drug Discovery
Animal
Studies
Clinical Tests
Commercialization

25. Synthetic DNA as Drugs

26. Why Can DNA Be Used as Drugs? The Structure of DNA and RNA
Four bases in DNA and RNA
They are A, T (U in RNA), G and C
Genetic information is stored in the sequence of A, T, G, C in DNA
DNA double stranded
RNA double/single stranded
A pairs to T (U in RNA) only and G pairs to C only
DNA-DNA, RNA-RNA, DNA-RNA

27. Why Can DNA Be Used as Drugs? The Base Pairs
DNA-DNA: A-T, G-C
RNA-RNA: A-U, G-C
DNA-RNA: A-U, G-C

28. Why Can DNA Be Used as Drugs? The Central Dogma of Molecular Biology
DNA: double stranded, contains genetic information
RNA: single stranded
Protein: the function molecule of life, function determined by the sequence of amino acids

29. Why Can DNA Be Used as Drugs. How People Get Disease
Why Can DNA Be Used as Drugs? How People Get Disease? Mono-genetic disorder
Currently, a total of ~4,000 genetic disorders are known
Some are single genetic disorder
Changes (mutations) of the sequence of one gene (DNA)
Point mutation
Deletion
And more
List of genetic disorders at
The mutated genes produce proteins that cannot function properly, diseases occur
Examples: Sickle-cell anemia, Cystic fibrosis (1/3900, most common, difficult breathing, die in 20s-30s, no cure), Color blindness

30. Why Can DNA Be Used as Drugs. How People Get Disease
Why Can DNA Be Used as Drugs? How People Get Disease? Poly-genetic disorder
Mutations occur in many genes
Do not have a clear cut of inheritance
But do “run in families”
The mutated genes produce proteins that cannot function properly, diseases occur
Difficult (not impossible) to study and treat because direct cause is unknown
Examples: Heart disease, hypertension, diabetes, obesity, cancers, low IQ

31. Why Can DNA Be Used as Drugs. How People Get Disease
Why Can DNA Be Used as Drugs? How People Get Disease? Bacteria and virus infections
Smallpox
million deaths in 20th century
Eliminated by vaccination
HIV/AIDS
Human immunodeficiency virus/acquire immunodeficiency syndrome
Still taking many lives each year, in 2000, 2.8 million
Hepatitis B
0.1 million lives taken in 2000
Liver inflammation, vomiting, and rarely death, but can lead to cancer
Tuberculosis
Bacteria, mostly infect lung, but also other parts of body
In 2004, 1.7 million deaths

32. Why Can DNA Be Used as Drugs
Why Can DNA Be Used as Drugs? How to stop genetic disorder using DNA drugs?
Design a short DNA sequence that matches the sequence of mRNA that is transcribed from the mutated gene (which causes diseases)
The DNA drug binds to the mRNA (A-U, G-C)
The mRNA cannot be translated to protein
Because no disease-causing protein, disease is cured

33. Design DNAs that can stop the critical gene expressions
Why Can DNA Be Used as Drugs? How to stop diseases caused by microorganisms using DNA drugs?
Select one or more genes that are critical for the disease-causing bacteria or virus
Design DNAs that can stop the critical gene expressions
The bacteria or virus dies and diseases cured

34. Why Use Synthetic DNA?
Natural DNA will be digested by enzymes, and also can cause immune response
Synthetic DNA cannot be recognized by enzymes, so they are stable and may not cause immune response
So, synthetic DNA can selectively block gene expression