Lecture 1: How Drugs Work and What Makes a Good Drug Target


“A miracle drug is any drug that will do what the label says it will do.” – Eric Hodgins

Lecture Goals

After this class, you should:

  • Know how pharmaceutical drugs work
  • Know what makes a good drug target
  • Be able to research a protein and determine if it is a good drug target


  • How drugs work
  • What makes for a good protein drug target?
  • Established targets
  • Tools for studying a potential drug target

Glossary Terms

  • Target: A macromolecular object (e.g., a protein) that performs a biological function.
  • Ligand: A microscopic substance (e.g., a small molecule) that binds to another microscopic substance (e.g., a protein).
  • Drug Target: A target with a biological function specifically implicated in human health.
  • Drug: A ligand that binds to and alters the function of a drug target in ways that improve human health.


How drugs work

Drugs are ligands that bind to drug targets. A ligand could be:

  1. A small molecule (like aspirin).
  2. A biologic (often a protein) like insulin or a therapeutic antibody.

A drug target could be:

  1. A cell membrane.
  2. Nucleic acid (DNA or RNA).
  3. A protein.

In this class, we’ll focus on small-molecule ligands and protein drug targets.

Aspirin, a small-molecule drug.

Cystic fibrosis transmembrane conductance regulator, the target of the drug ivacaftor.

When drugs bind to their drug targets, they increase or decrease target function/accessibility/etc. in order to promote human health.

What makes for a good protein drug target?

Drug targets include enzymes, ion channels, transporters, and receptors (both extracellular and nuclear).

Good target characteristics:

  1. Plays an essential (non-redundant) role in a health-related process.
  2. Can be modulated without killing people. (Killing the patient cures all disease…)
  3. Has a sufficiently unique structure.
    • Want to inhibit an essential parasite protein? Do human cells rely on an (almost) identical protein?
    • Want to inhibit a human protein with an ATP-bindng pocket? How many other proteins bind ATP?
  4. Has a known molecular structure to enable structure-based (computer-aided) drug design.
  5. Acts through a defined (small-molecule) active site. Protein-protein interfaces are very hard to disrupt.

    Influenza neuraminidase, with its druggable active site.

    Cytokine receptor complex (multiple proteins come together, binding via surfaces rather than pockets).

Other issues to consider:

  1. Established targets:
  2. New targets:

Established targets

Established targets have been extensively studied. As of 2011, researchers had identified 435 targets with activities affected by 989 unique drugs.

1. DRUGBANK: Targets of approved and experimental drugs.
2. BindingDB

Tools for studying a potential drug target




  • How drugs work
  • What makes for a good protein drug target?
  • Established targets
  • Tools for studying a potential drug target

Preview: Next Class

If you want to study ahead, the goals of our next class will be:

  • Know about protein structure
  • Be able to visualize a protein in your browser


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