Pharmacology/Part 1

Part 1: Foundations of Pharmacology

From the initial discovery of a potential drug molecule to an approved medicine is one of the most challenging endeavors in science. This part covers drug discovery, development, clinical trials, and the regulatory process that brings medicines to patients.

📊 The Drug Development Challenge

10-15
Years to develop
$1-2B
Average cost
<10%
Clinical success rate
~50
New drugs/year (FDA)

📜Historical Milestones

1806
Morphine isolated from opium
First pure drug compound isolated
1899
Aspirin synthesized (Bayer)
First mass-produced synthetic drug
1928
Penicillin discovered (Fleming)
Beginning of antibiotic era
1952
Chlorpromazine for schizophrenia
Birth of psychopharmacology
1960
Oral contraceptive approved
Revolutionized reproductive health
1987
Prozac (fluoxetine) approved
First SSRI antidepressant
1998
Herceptin (trastuzumab) approved
Targeted cancer therapy era begins
2020
mRNA COVID vaccines
Fastest vaccine development in history

🧪Drug Development Pipeline Simulator

Discovery
2-4 years
Preclinical
1-2 years
Phase I
1-2 years
Phase II
2-3 years
Phase III
3-4 years
FDA Review
1-2 years
Approved!
—
10,000compounds

Current Phase

Discovery

Target identification, HTS, lead optimization

Compounds
10,000
Years
0
Cost ($M)
0
Note: Only ~1 in 10,000 discovered compounds becomes an approved drug. The entire process typically takes 10-15 years and costs $1-2 billion.

🎯Drug Target Classes Explorer

34%25%15%10%8%8%DrugTargets

🔬Drug Discovery Process

1. Target Identification

Identify a biological target (protein, enzyme, receptor) involved in disease.

  • • Genomics and proteomics
  • • GWAS (genome-wide association studies)
  • • Pathway analysis
  • • Literature mining

2. Target Validation

Confirm that modulating the target affects disease.

  • • Knockout/knockdown studies
  • • Animal disease models
  • • Human genetic evidence
  • • Tool compound studies

3. Hit Discovery

Find molecules that interact with the target.

  • • High-throughput screening (HTS)
  • • Virtual/computational screening
  • • Fragment-based drug discovery
  • • Natural product screening

4. Lead Optimization

Improve potency, selectivity, and drug-like properties.

  • • Structure-activity relationships (SAR)
  • • Medicinal chemistry modifications
  • • ADMET optimization
  • • Selectivity profiling

📏Lipinski's Rule of Five Calculator

Lipinski's Rule of Five predicts oral bioavailability. A compound is likely to be orally active if it violates no more than one of these rules.

400 ✓
100≤ 500800
3.0 ✓
-2≤ 58
3 ✓
0≤ 510
6 ✓
0≤ 1015
✓
Likely Orally Bioavailable
0 violations of 4 rules

The Rules:

  • • MW ≤ 500 Da
  • • LogP ≤ 5
  • • H-bond donors ≤ 5
  • • H-bond acceptors ≤ 10

🏥Clinical Trial Phases

PhaseParticipantsPurposeDurationSuccess Rate
Phase I20-100 healthy volunteersSafety, dosing, pharmacokineticsSeveral months~70%
Phase II100-500 patientsEfficacy, side effects, optimal dose1-2 years~33%
Phase III1000-5000 patientsConfirm efficacy, monitor adverse events2-4 years~50%
Phase IVThousands (post-marketing)Long-term safety, new indicationsOngoing—

🏛️Regulatory Agencies

FDA

United States

NDA/BLA → Advisory Committee → Approval

EMA

European Union

MAA → CHMP → European Commission

PMDA

Japan

JNDA → Expert Discussion → Approval

Topics in This Part

1.1

Introduction & History

From ancient remedies to modern drug design; key milestones in pharmacology

1.2

Drug Discovery

Target identification, high-throughput screening, lead optimization

1.3

Drug Development

Preclinical studies, toxicology, formulation, manufacturing

1.4

Clinical Trials

Phase I-IV trials, study design, endpoints, bioethics

1.5

Regulatory Approval

FDA, EMA, NDA/BLA submission, post-marketing surveillance

← Pharmacology OverviewPart 2: Pharmacokinetics →