Editing Drug design (section)

== 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 is 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 [[QSAR|structure-based drug design]] leading to an approved drug is the carbonic anhydrase inhibitor [[dorzolamide]], which was approved in 1995.<ref name="pmid8164249">{{cite journal | vauthors = Greer J, Erickson JW, Baldwin JJ, Varney MD | title = Application of the three-dimensional structures of protein target molecules in structure-based drug design | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 8 | pages = 1035–1054 | date = April 1994 | pmid = 8164249 | doi = 10.1021/jm00034a001 }}</ref><ref name="isbn3-527-29343-4">{{cite book | vauthors = Timmerman H, Gubernator K, Böhm HJ, Mannhold R, Kubinyi H | title = Structure-based Ligand Design (Methods and Principles in Medicinal Chemistry) | publisher = Wiley-VCH | location = Weinheim | year = 1998 | isbn = 978-3-527-29343-8 | name-list-style = vanc }}</ref>

Another 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 [[leukemia]]s ([[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.<ref>{{cite journal | vauthors = Capdeville R, Buchdunger E, Zimmermann J, Matter A | title = Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug | journal = Nature Reviews. Drug Discovery | volume = 1 | issue = 7 | pages = 493–502 | date = July 2002 | pmid = 12120256 | doi = 10.1038/nrd839 | s2cid = 2728341 }}</ref>

Additional examples include:

{{div col|colwidth=20em}}
* Many of the [[atypical antipsychotic]]s
* [[Cimetidine]], the prototypical [[H2-receptor antagonist|H<sub>2</sub>-receptor antagonist]] from which the later members of the class were developed
* Selective [[Cyclooxygenase|COX-2]] inhibitor [[NSAID]]s
* [[Enfuvirtide]], a peptide HIV entry inhibitor
* [[Nonbenzodiazepines]] like [[zolpidem]]  and [[zopiclone]]
* [[Raltegravir]], an [[HIV integrase]] inhibitor<ref name="url_AutoDock_Integrase_Inhibitor">{{cite web | url = http://autodock.scripps.edu/news/autodocks-role-in-developing-the-first-clinically-approved-hiv-integrase-inhibitor | title = AutoDock's role in Developing the First Clinically-Approved HIV Integrase Inhibitor | date = 2007-12-17 | work = Press Release | publisher = The Scripps Research Institute }}</ref>
* [[Selective serotonin reuptake inhibitor|SSRIs]] (selective serotonin reuptake inhibitors), a class of [[antidepressant]]s
* [[Zanamivir]], an [[antiviral drug]]
{{Div col end}}