Turning a disease into a medicine is a long, lossy journey — roughly 10–15 years, US$1–2.6 billion, and only about 1 in 5,000–10,000 screened compounds ever reaches the market. The pipeline below is the road every drug travels.
Stages of drug discovery
- Target identification — pick a biomolecule (receptor, enzyme, ion channel, transporter, nucleic acid) implicated in the disease.
- Target validation — confirm its role using knockout/knockdown, antibodies and disease models.
- Hit identification — screen libraries by high-throughput screening (HTS), virtual/in-silico screening, fragment- or structure-based design, or natural products.
- Lead identification — confirm and select compounds with genuine, reproducible activity.
- Lead optimisation — use structure–activity relationship (SAR) medicinal chemistry to improve potency, selectivity, ADME and safety.
- Candidate selection — choose a drug candidate for preclinical development.
Approaches to finding drugs
- Target-based (rational) vs phenotypic (function-based) screening.
- High-throughput screening (HTS), rational/structure-based design and computer-aided drug design (CADD).
- Combinatorial chemistry, fragment-based discovery, natural-product screening, and drug repurposing.
Preclinical development
- In-vitro (cell/tissue) and in-vivo (animal) studies.
- Pharmacology (PD), pharmacokinetics/ADME and toxicology (acute, sub-chronic, chronic, genotoxicity, reproductive, carcinogenicity).
- Establishes safety, dose range and proof of concept before human testing — under GLP; animal studies in India follow CPCSEA.
From candidate to market
File for clinical-trial permission (India: CDSCO / NDCT 2019; US: IND) → clinical trials Phase I → II → III (safety → efficacy/dose → confirmatory) → marketing approval (New Drug Application) → Phase IV post-marketing surveillance.
Drug-likeness: Lipinski’s Rule of Five
An orally active, drug-like molecule usually has MW ≤ 500, logP ≤ 5, ≤ 5 H-bond donors and ≤ 10 H-bond acceptors — used to filter leads early.
Sources of drugs
Natural (plants, microbes, animals, minerals); synthetic/semi-synthetic chemistry; and biotechnology (recombinant proteins, monoclonal antibodies, vaccines).
Exam tip: recite the pipeline — target ID → validation → hit → lead → optimisation → candidate → preclinical → clinical → approval → Phase IV — and quote the numbers (~10–15 years, ~1 in 5,000–10,000). Don’t forget Lipinski’s Rule of Five and GLP/CPCSEA for preclinical work.
Drug discovery is a funnel: thousands of molecules in, one medicine out. Learn the stages and the filters, and the long road from a biological target to an approved drug becomes a clear sequence you can describe in any exam.