Structural biology of insulin and IGF1 receptors: implications for drug design

Nat Rev Drug Discov. 2002 Oct;1(10):769-83. doi: 10.1038/nrd917.


Type 2 diabetes mellitus -- in which the body produces insufficient amounts of insulin or the insulin that is produced does not function properly to control blood glucose -- is an increasingly common disorder. Prospective clinical studies have proven the benefits of tighter glucose control in reducing the frequency and severity of complications of the disease, leading to the advocation of earlier and more aggressive use of insulin therapy. Given the reluctance of patients with type 2 diabetes to inject themselves with insulin, orally active insulin mimetics would be a major therapeutic advance. Here, we discuss recent progress in understanding the structure-function relationships of the insulin and insulin-like growth factor 1 (IGF1) receptors, their mechanism of activation and their implications for the design of insulin-receptor agonists for diabetes therapy and IGF1-receptor antagonists for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Design*
  • Humans
  • Receptor, IGF Type 1 / agonists
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / chemistry*
  • Receptor, Insulin / agonists
  • Receptor, Insulin / antagonists & inhibitors
  • Receptor, Insulin / chemistry*
  • Structure-Activity Relationship


  • Receptor, IGF Type 1
  • Receptor, Insulin