Targeting cancer: the challenges and successes of structure-based drug design against the human purinome.
Purine-binding proteins are of critical importance to all living organisms. Approximately 13% of the human genome is devoted to coding for purine-binding proteins. Given their importance, purine-binding proteins are attractive targets for chemotherapeutic intervention against a variety of disease states, particularly cancer. Modern computational and biophysical techniques, combined together in a structure-based drug design approach, aid immensely in the discovery of inhibitors of these targets. This review covers the process of modern structure-based drug design and gives examples of its use in discovery and development of drugs that target purine-binding proteins. The targets reviewed are human purine nucleoside phosphorylase, human epidermal growth factor receptor kinase, and human kinesin spindle protein.
Knapp
Mark
M
Chiron Corporation, Computational Chemistry and Structural Chemistry, Biopharma Research, 4560 Horton Street, M/S 4.4, Emeryville, CA 94608-2916, USA.
Bellamacina
Cornelia
C
Murray
Jeremy M
JM
Bussiere
Dirksen E
DE
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D011685:Purine Nucleotides / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D008024:Ligands; D020543:Proteome; D011685:Purine Nucleotides