NAAG peptidase inhibitors and their potential for diagnosis and therapy.
Modulation of N-acetyl-L-aspartyl-L-glutamate peptidase activity with small-molecule inhibitors holds promise for a wide variety of diseases that involve glutamatergic transmission, and has implications for the diagnosis and therapy of cancer. This new class of compounds, of which at least one has entered clinical trials and proven to be well tolerated, has demonstrated efficacy in experimental models of pain, schizophrenia, amyotrophic lateral sclerosis, traumatic brain injury and, when appropriately functionalized, can image prostate cancer. Further investigation of these promising drug candidates will be needed to bring them to the marketplace. The recent publication of the X-ray crystal structure for the enzymatic target of these compounds should facilitate the development of other new agents with enhanced activity that could improve both the diagnosis and treatment of neurological disorders.
Zhou
Jia
J
Acenta Discovery, Inc., 9030 South Rita Road, Suite 300, Tucson, Arizona 85747, USA. jia.zhou@acentadiscovery.com
Neale
Joseph H
JH
Pomper
Martin G
MG
Kozikowski
Alan P
AP
D000818:Animals; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D011480:Protease Inhibitors / Q000737:chemistry / Q000627:therapeutic use*
D011480:Protease Inhibitors; D043425:Glutamate Carboxypeptidase II