What is Medicinal Chemistry (section 2)

 Section 2: The Process of Drug Discovery

Drug discovery is the process of finding new medicines to treat diseases. It is a long and detailed process that involves many steps. Medicinal chemists, pharmacologists, toxicologists, and other scientists work together in this process. The goal is to identify a compound that can interact with the body to treat a disease and then make sure it is safe and effective.

Let’s go step by step through the drug discovery process.

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1. Disease Understanding (Target Identification)

The first step in drug discovery is to understand the disease at the molecular level. Scientists study how the disease develops, what changes happen in the body, and which molecules are involved. These molecules are usually proteins, enzymes, or receptors.

Once a disease-causing molecule is identified, it becomes a drug target. For example, in cancer, a certain protein might be overactive. In infections, a bacterial enzyme might be necessary for the bacteria to survive. Blocking these can help cure or control the disease.

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2. Target Validation

After identifying the target, researchers check whether this target is actually important in the disease process. This is called target validation. It is done using:

• Cell experiments
• Animal models
• Genetic studies

If blocking or modifying this target improves the disease condition in the test models, the target is considered valid.

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3. Hit Identification

Once the target is validated, the next step is to find a chemical compound (called a “hit”) that interacts with the target.

This is done using methods such as:

a. High-Throughput Screening (HTS)

Thousands of chemical compounds are tested against the target using automated machines to see if any compound binds to it or affects its activity.

b. Virtual Screening

Computer models simulate the interaction between molecules and the target protein. It is faster and cheaper than lab testing.

c. Natural Products Screening

Compounds from plants, microbes, or marine organisms are tested. Many useful drugs like penicillin and paclitaxel came from natural sources.

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4. Hit to Lead Optimization

A “hit” is a compound that shows some desired activity. But it may not be strong, selective, or safe. So, chemists modify the structure of the hit compound to improve its activity. This process is called lead optimisation.

During this stage, scientists try to improve:

• Potency: How strongly it works
• Selectivity: How specifically it targets only the disease-causing molecule
• Solubility: Whether it can dissolve in body fluids
• Stability: Whether it remains stable in the body
• Toxicity: Whether it causes side effects

The improved compound is now called a lead compound.

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5. Preclinical Testing

Now that we have a lead compound, it must be tested for safety and effectiveness in laboratory and animal studies before testing in humans. This is known as preclinical testing.

It involves:

a. In-vitro studies

• Tests on cell cultures
• Helps understand how the drug works on a molecular level

b. In-vivo studies

• Tests on animals like rats or mice
• Checks for how the drug is absorbed, metabolised, and excreted
• Monitors for any side effects or toxicity

If results are promising, the drug can proceed to human testing.

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6. Investigational New Drug (IND) Application

Before starting clinical trials in humans, a company must submit an IND application to the regulatory agency (e.g., US FDA, CDSCO in India).

This application includes:

• Data from preclinical studies
• Manufacturing details
• Plans for human trials
• Safety information

If the regulatory body approves, human trials can begin.

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7. Clinical Trials (Human Studies)

Clinical trials are conducted in three main phases:

Phase I:

• Conducted on a small group of healthy volunteers (20–100 people)
• Tests for safety, dose tolerance, and side effects

Phase II:

• Conducted on patients who have the disease (100–500 people)
• Tests for effectiveness and monitors side effects
• Helps determine the optimal dose

Phase III:

• Conducted on a larger group of patients (1000+ people)
• Confirms effectiveness
• Compares with existing treatments
• Monitors for rare side effects

If successful, the data is compiled and submitted to the regulatory body.

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8. New Drug Application (NDA) / Marketing Authorisation

After clinical trials are completed, the company submits a New Drug Application (NDA) in the US or a Marketing Authorisation Application (MAA) in Europe or India.

The application includes:

• All study results
• Manufacturing process
• Labelling and packaging information
• Proposed price and usage details

If approved, the drug can be sold in the market.

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9. Post-Marketing Surveillance (Phase IV)

Even after approval, the drug is monitored in the market. This is called pharmacovigilance or Phase IV studies. It helps:

• Track long-term side effects
• Identify rare or delayed reactions
• Ensure continued safety

If major issues arise, the drug may be withdrawn or its use restricted.

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10. Generic Drug Development

After the patent of the original drug expires (usually 20 years), other companies can make generic versions of the drug. Generics must show bioequivalence — that they work the same as the original drug — but they are cheaper.

This helps improve access to medicine for more people.

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Summary Table: Steps in Drug Discovery

Stage	Purpose	Key Activities
Disease Understanding	Find cause of disease	Molecular and genetic studies
Target Identification	Choose a protein to act upon	Protein analysis, literature research
Target Validation	Confirm importance of target	Lab tests, animal studies
Hit Identification	Find molecules that affect target	HTS, virtual screening, natural screening
Lead Optimization	Improve properties of hit compounds	Chemical modifications, SAR studies
Preclinical Testing	Test safety and action in animals/lab	In-vitro and in-vivo testing
Clinical Trials (Phases I-III)	Human testing for safety and effectiveness	Trials in volunteers and patients
NDA / MAA Filing	Get permission to market the drug	Regulatory submissions
Post-Marketing Surveillance	Monitor long-term safety	Real-world data collection

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Conclusion

The drug discovery process is long, complex, and costly. It can take 10–15 years and cost billions of rupees to bring one new drug to the market. However, it is a necessary process to ensure that drugs are safe, effective, and of good quality. As pharmacy students, understanding this process helps you appreciate the efforts behind every tablet, injection, or syrup you see in a pharmacy.