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.

[3dmoljs pdb=”https://durrantlab.pitt.edu/teaching_files/models/aspirin.pdb” caption=”Aspirin, a small-molecule drug.” solidligand=”false” zoomtarget=”ligand” position=”left”][3dmoljs pdb=”5UAK” caption=”Cystic fibrosis transmembrane conductance regulator, the target of the drug ivacaftor.” solidligand=”false” zoomtarget=”protein” position=”right”]

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.
    [3dmoljs pdb=”2HU4″ chain=”A” caption=”Influenza neuraminidase, with its druggable active site.” solidligand=”false” zoomtarget=”ligand” position=”left”][3dmoljs pdb=”5J12″ caption=”Cytokine receptor complex (multiple proteins come together, binding via surfaces rather than pockets).” solidligand=”false” zoomtarget=”receptor” position=”right” surfcolor=”chain”]

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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