What is Medicinal Chemistry (section 5)

Section 5: Drug Targets – Types

A drug target is a specific molecule in the body that a medicine acts upon to bring about a therapeutic effect. In modern drug discovery, identifying the right target is one of the most important steps. These targets are usually proteins, enzymes, DNA, RNA, or cell receptors that play key roles in disease processes.

Understanding what drug targets are and how they work helps scientists design better, more specific medicines with fewer side effects. This section will introduce the types of drug targets in the body and their significance in medicinal chemistry.

---

1. What is a Drug Target?

A drug target is any biological molecule in the body that is linked to a disease process. When a drug binds to or modifies this molecule, it can either:

• Stop the disease from progressing,
• Reduce symptoms,
• Or cure the condition.

The interaction between a drug and its target is often compared to a lock and key. The drug is the key, and the target is the lock. A perfect fit leads to the desired action.

---

2. Criteria for a Good Drug Target

An ideal drug target should:

• Be clearly involved in the disease
• Be present in the affected tissues
• Be “druggable” (i.e., able to bind to small molecules)
• Have minimal presence in healthy tissues to avoid side effects

---

3. Types of Drug Targets

There are several types of drug targets. The most common ones are:

A. Enzymes

Enzymes are proteins that speed up chemical reactions in the body. If a particular enzyme is overactive in a disease, a drug can inhibit it.

Examples:

• ACE (Angiotensin-Converting Enzyme): Converts angiotensin I to angiotensin II, which raises blood pressure. Drugs like enalapril inhibit ACE to treat hypertension.
• Cyclooxygenase (COX): Converts arachidonic acid to prostaglandins (inflammation). Inhibited by aspirin and ibuprofen.
• HMG-CoA Reductase: Helps make cholesterol in the liver. Inhibited by statins (like atorvastatin).

Drug action on enzymes includes:

• Competitive inhibition
• Non-competitive inhibition
• Irreversible inhibition

---

B. Receptors

Receptors are protein structures found on the surface of cells. They receive signals from the environment (like hormones or neurotransmitters) and start a biological response.

Drugs can:

• Activate the receptor (agonists)
• Block the receptor (antagonists)

Examples:

• β1-Adrenergic Receptor: Found in the heart. Blocked by atenolol to reduce heart rate and blood pressure.
• Histamine H1 Receptor: Found in allergy pathways. Blocked by antihistamines like cetirizine.
• Dopamine Receptors: Found in the brain. Targeted in Parkinson’s and schizophrenia.

---

C. Ion Channels

Ion channels control the movement of ions (like Na⁺, K⁺, Ca²⁺) across cell membranes. This movement is essential for nerve impulses, muscle contraction, and heart rhythm.

Drugs can:

• Open ion channels
• Block ion channels

Examples:

• Calcium Channel Blockers (e.g., amlodipine): Lower blood pressure.
• Sodium Channel Blockers (e.g., lidocaine): Used as local anaesthetics.
• Potassium Channel Openers (e.g., minoxidil): Used to treat hypertension and hair loss.

---

D. Transport Proteins (Carriers)

Transport proteins carry substances like glucose, ions, or drugs across cell membranes. Blocking or enhancing these carriers can help in disease treatment.

Examples:

• Proton Pump (H⁺/K⁺ ATPase): Found in the stomach lining. Inhibited by omeprazole to reduce acid.
• SGLT2 Transporters: Found in the kidneys. Blocked by dapagliflozin in diabetes to reduce blood sugar.

---

E. Nucleic Acids (DNA/RNA)

Some drugs act directly on the genetic material (DNA or RNA) of cells. This is common in cancer and antiviral therapies.

Examples:

• Cisplatin: Binds to DNA and stops cancer cell division.
• Ribavirin: Affects viral RNA.
• Antisense Therapy: Uses short RNA pieces to block the translation of disease-causing proteins.

---

F. Structural Proteins

These are proteins that provide support to the cell. In some diseases, targeting structural proteins can destroy harmful cells.

Example:

• Tubulin: Forms microtubules in cells. Targeted by anticancer drugs like vincristine and paclitaxel to stop cancer cell division.

---

G. Hormone Targets

Hormones are chemical messengers. Some drugs target hormone production or hormone receptors.

Examples:

• Insulin Receptor: Targeted by insulin in diabetes.
• Oestrogen Receptor: Targeted by tamoxifen in breast cancer.
• Thyroid Hormone Replacement: Used in hypothyroidism (e.g., levothyroxine).

---

4. Summary Table – Types of Drug Targets

Target Type	Examples of Targets	Example Drugs	Uses
Enzymes	ACE, COX, HMG-CoA reductase	Enalapril, Aspirin, Statins	Hypertension, Inflammation
Receptors	β1, H1, Dopamine receptors	Atenolol, Cetirizine	Heart, Allergy, Brain
Ion Channels	Na⁺, Ca²⁺, K⁺ channels	Lidocaine, Amlodipine	Anaesthesia, Hypertension
Transport Proteins	Proton pump, SGLT2	Omeprazole, Dapagliflozin	Acidity, Diabetes
Nucleic Acids	DNA, RNA	Cisplatin, Ribavirin	Cancer, Viral infections
Structural Proteins	Tubulin	Paclitaxel, Vincristine	Cancer
Hormones and Receptors	Insulin, Estrogen, Thyroid hormone	Insulin, Tamoxifen, Thyroxine	Diabetes, Cancer, Thyroid

---

5. How Do Drugs Interact with Targets?

Drugs interact with their targets through:

• Hydrogen bonds
• Ionic bonds
• Hydrophobic interactions
• Covalent bonds (rare, often irreversible)

The shape and chemical structure of the drug must match the target for effective binding. This is the basis for Structure–Activity Relationship (SAR) in medicinal chemistry.

---

6. Drug Selectivity and Specificity

A good drug should:

• Bind only to the desired target (high specificity)
• Have minimal interaction with other proteins (high selectivity)

If a drug binds to many different targets, it may cause side effects. This is called off-target binding.

---

7. Importance of Understanding Drug Targets

For pharmacists and medicinal chemists, knowing the drug targets helps in:

• Explaining how a drug works
• Predicting possible side effects
• Choosing alternative drugs if resistance occurs
• Designing new drugs for emerging diseases

---

Conclusion

Drug targets are at the heart of medicinal chemistry and pharmacology. By understanding the different types of targets — from enzymes and receptors to DNA and structural proteins — we can design medicines that are effective, specific, and safe. As science advances, we continue to discover new targets and develop better therapies for both common and rare diseases.