The ATPases: a new family for a family-based drug design approach.
The rapid discovery of new drugs is greatly facilitated when a family of related proteins is targeted with a similar approach in chemistry. Few protein families have so far been investigated using this kind of 'family-based' approach. Therefore, to increase the size of our Pharmacopeia and to cure human diseases more efficiently, new druggable protein families must be identified. It is shown in this review that ATPases are very good candidates for a family-based approach. The human proteome contains many ATPases, which are involved in several diseases. All the ATPases contain a nucleotide-binding site, and it is therefore possible to target all of them with a single strategy in chemistry; the design of competitive ATP inhibitors. Moreover, because a similar approach has been conducted with the protein kinases, the compound libraries and the knowledge developed in the kinase field can be directly applied to the ATPases.
Chène
Patrick
P
Novartis, K125 442, CH-4002 Basel, Switzerland. patrick_chene@yahoo.com
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D004265:DNA Helicases / Q000502:physiology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000502:physiology; D008958:Models, Molecular; D005810:Multigene Family; D011487:Protein Conformation; D020365:RNA Helicases / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D020365:RNA Helicases; D016547:Kinesins