Drug Design - Examples

Examples

A particular example of rational drug design involves the use of three-dimensional information about biomolecules obtained from such techniques as X-ray crystallography and NMR spectroscopy. Computer-aided drug design in particular becomes much more tractable when there's a high-resolution structure of a target protein bound to a potent ligand. This approach to drug discovery is sometimes referred to as structure-based drug design. The first unequivocal example of the application of structure-based drug design leading to an approved drug is the carbonic anhydrase inhibitor dorzolamide, which was approved in 1995.

Another important case study in rational drug design is imatinib, a tyrosine kinase inhibitor designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosome-positive leukemias (chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous drugs for cancer, as most agents of chemotherapy simply target rapidly dividing cells, not differentiating between cancer cells and other tissues.

Additional examples include:

• Many of the atypical antipsychotics
• Cimetidine, the prototypical H₂-receptor antagonist from which the later members of the class were developed
• Selective COX-2 inhibitor NSAIDs
• Dorzolamide, a carbonic anhydrase inhibitor used to treat glaucoma
• Enfuvirtide, a peptide HIV entry inhibitor
• Nonbenzodiazepines like zolpidem and zopiclone
• Probenecid
• SSRIs (selective serotonin reuptake inhibitors), a class of antidepressants
• Zanamivir, an antiviral drug
• Isentress, HIV Integrase inhibitor

Case studies

• 5-HT3 antagonists
• Acetylcholine receptor agonists
• Angiotensin receptor blockers
• Bcr-Abl tyrosine kinase inhibitors
• Cannabinoid receptor antagonists
• CCR5 receptor antagonists
• Cyclooxygenase 2 inhibitors
• Dipeptidyl peptidase-4 inhibitors
• HIV protease inhibitors
• NK1 receptor antagonists
• Non-nucleoside reverse transcriptase inhibitors
• Proton pump inibitors
• Triptans
• TRPV1 antagonists
• Renin inhibitors
• c-Met inhibitors