What is Medicinal Chemistry (section 4)
Section 4: Modern Drug Discovery
Modern drug discovery is a
systematic, science-driven process that uses advanced technologies, computers,
and biological knowledge to develop new and better medicines. It is more
efficient, safer, and faster than older methods. In this section, you will
learn how modern science has transformed the way we find new drugs and bring
them to patients.
1.
What Is Modern Drug Discovery?
Modern drug discovery means using
tools like:
- Computers (in-silico methods)
- Genetic and protein information (genomics and
proteomics)
- High-throughput screening
- Data analysis using AI and machine learning
- Target-based design
This approach saves time, reduces
costs, and increases the chances of finding safe and effective medicines.
2.
Key Features of Modern Drug Discovery
Modern drug discovery is
characterised by:
a.
Target-Based Approach
Instead of randomly testing
substances, scientists first identify a biological target (usually a protein or
enzyme) that plays a key role in a disease. The drug is then designed to
interact with this target.
b.
Rational Drug Design
Using knowledge of chemistry and
biology, scientists design molecules that fit the target like a key fits a
lock. This is faster and more specific than traditional methods.
c.
Structure-Based Drug Design (SBDD)
Scientists use 3D models of target
proteins (from X-ray crystallography or NMR) to design drugs that fit their
structure.
d.
High-Throughput Screening (HTS)
Thousands of compounds are tested
quickly using machines and robots to see if they affect the target. Positive
results are called “hits”.
e.
Combinatorial Chemistry
Many different compounds are made by
combining sets of chemical building blocks. This increases the number of
compounds available for testing.
f.
Bioinformatics and Computer Modelling
Computers simulate how a drug might
behave in the body. This helps avoid side effects and reduces the need for
animal testing in early stages.
3.
Steps in Modern Drug Discovery
Although the basic steps of drug
discovery remain the same, modern techniques have made each step more advanced
and precise.
Step
1: Target Identification and Validation
- Use gene sequencing and protein studies to identify
potential targets.
- Confirm that changing the activity of this target will
affect the disease.
Step
2: Lead Compound Discovery
- Use HTS, virtual screening, or data mining to identify
promising compounds.
- These are “hits” which are further optimised.
Step
3: Lead Optimisation
- Modify chemical structure to improve potency,
selectivity, and safety.
- Evaluate properties like solubility, stability, and
absorption.
Step
4: Preclinical Studies
- Conduct in-vitro (cell culture) and in-vivo (animal)
testing.
- Study drug absorption, distribution, metabolism,
excretion, and toxicity (ADMET).
Step
5: Clinical Trials
- Test in humans (Phase I, II, III) to assess safety and
effectiveness.
Step
6: Regulatory Review and Approval
- Submit data to regulatory agencies (like FDA, CDSCO)
for marketing approval.
Step
7: Post-Marketing Surveillance
- Continue monitoring the drug in real-world conditions
for rare or long-term side effects.
4.
Technologies Used in Modern Drug Discovery
a.
Genomics and Proteomics
- Genomics: Study of genes to identify disease-related
mutations.
- Proteomics: Study of proteins, especially those involved
in disease pathways.
These help identify novel drug
targets and biomarkers.
b.
Molecular Modelling
- Uses computer software to model drug-target
interactions.
- Predicts how a molecule will fit and bind to the
target.
c.
Quantitative Structure–Activity Relationship (QSAR)
- Mathematical models that link the structure of a
molecule to its biological activity.
- Helps predict how effective a new compound might be.
d.
Artificial Intelligence (AI) and Machine Learning
- AI systems analyse millions of molecules and predict
which ones are most likely to succeed.
- Saves time and avoids unnecessary experiments.
e.
Pharmacogenomics
- Studies how a person’s genetic makeup affects their
response to drugs.
- Helps develop personalised medicines.
5.
Examples of Success in Modern Drug Discovery
Some of the most successful modern
drugs have come from rational design and target-based discovery:
- Imatinib (Gleevec):
Designed to target a specific protein in cancer cells (used in chronic
myeloid leukemia).
- Oseltamivir (Tamiflu):
Designed to inhibit a flu virus protein.
- HIV Protease Inhibitors: Designed to block a key enzyme in HIV replication.
- Monoclonal Antibodies:
Designed to target proteins involved in cancer or immune disorders (e.g.,
trastuzumab for breast cancer).
6.
Advantages of Modern Drug Discovery
|
Feature |
Benefit |
|
Target-specific design |
Reduces side effects |
|
Faster screening |
Saves time |
|
Use of AI and modelling |
Cuts costs |
|
Improved safety prediction |
Fewer failures in clinical trials |
|
Personalised drug development |
More effective treatment for
individuals |
7.
Challenges in Modern Drug Discovery
Despite its power, modern drug
discovery still faces challenges:
- High cost:
Can cost over ₹1000 crores to develop one drug.
- Time-consuming:
Even with fast screening, approval takes 10–12 years.
- High failure rate:
Many compounds fail in clinical trials due to side effects or poor
results.
- Ethical concerns:
Testing on animals and humans must be carefully monitored.
- Antibiotic resistance and rare diseases: Still difficult to treat despite modern techniques.
8.
Drug Repurposing: A Modern Strategy
Drug repurposing means finding new
uses for old drugs. It is faster and cheaper than developing a new drug.
Example:
- Thalidomide:
Once banned, now used for multiple myeloma.
- Hydroxychloroquine:
Originally for malaria, repurposed for COVID-19 trials.
9.
Future Trends in Drug Discovery
The future of modern drug discovery
lies in:
- Gene therapy:
Editing faulty genes to treat diseases.
- RNA-based drugs:
Like mRNA vaccines (Pfizer, Moderna for COVID-19).
- Nano-medicines:
Drug delivery using nanoparticles.
- Lab-on-a-chip:
Miniature labs to test drugs quickly.
- Synthetic biology:
Designing cells to produce useful compounds.
Summary
Table
|
Modern
Concept |
Purpose |
|
Target-Based Design |
Select a specific protein or gene
to act on |
|
High-Throughput Screening |
Test thousands of compounds
rapidly |
|
Molecular Modelling |
Simulate drug–target interactions |
|
QSAR |
Predict activity from chemical
structure |
|
Pharmacogenomics |
Personalised medicine |
|
AI and Big Data |
Smart analysis of drug data |
|
Drug Repurposing |
Find new uses for known drugs |
Conclusion
Modern drug discovery is more
scientific, structured, and technology-driven than ever before. It has made
drug development faster, more precise, and less risky. As students of pharmacy,
understanding this approach will prepare you to participate in cutting-edge
research and innovation in the pharmaceutical industry. You will be able to
appreciate the role of technology, data, and interdisciplinary knowledge in
creating the medicines of tomorrow.
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