Pharmacophore identification: the case of the ser/thr protein phosphatase inhibitors.
This review provides a chronological account of the identification and refinement of the pharmacophore for inhibition of two key serine/threonine protein phosphatases, PP1 and PP2A. The dramatic impact of natural product isolation, molecular modeling, analogue design, biochemical studies, and crystallography on the evolution of the pharmacophore will be described.
Colby
David A
DA
Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA.
Chamberlin
A Richard
AR
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000266:history* / Q000494:pharmacology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000266:history*; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry
D004791:Enzyme Inhibitors; D013912:Threonine; D012694:Serine; D010749:Phosphoprotein Phosphatases