Design and synthesis of selective inhibitors of placental alkaline phosphatase.
Placental Alkaline Phosphatase (PLAP) is a tissue-restricted isozyme of the Alkaline Phosphatase (AP) superfamily. PLAP is an oncodevelopmental enzyme expressed during pregnancy and in a variety of human cancers, but its biological function remains unknown. We report here a series of catechol compounds with great affinity for the PLAP isozyme and significant selectivity over other members of the AP superfamily. These selective PLAP inhibitors will provide small molecule probes for the study of the pathophysiological role of PLAP.
Lanier
Marion
M
Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121-2804, USA. mlanier@hbri.org
Sergienko
Eduard
E
Simão
Ana Maria
AM
Su
Ying
Y
Chung
Thomas
T
Millán
José Luis
JL
Cashman
John R
JR
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002396:Catechols; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental; C034221:catechol