title: PD 90780, a non peptide inhibitor of nerve growth factor's binding to the P75 NGF receptor.
abstract: Nerve growth factor is a peptide that supports the survival and differentiation of discrete neuronal populations in the peripheral and central nervous systems. NGF binds to both trkA, a tyrosine kinase receptor, and to the p75 nerve growth factor receptor, a protein lacking a consensus signalling sequence. We have identified a substituted pyrazoloquinazolinone, PD 90780, which inhibits binding of nerve growth factor to the p75 receptor. This inhibition of binding occurs due to PD 90780 binding to nerve growth factor, not to the p75 receptor. This compound may be useful in identifying the region(s) of nerve growth factor involved in binding to the p75 receptor and in clarifying the role of p75 receptor in the actions of the neurotrophins.
authors.affiliation: Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48106, USA.
authors.forename: K
authors.initials: K
authors.lastname: Spiegel
authors.forename: D
authors.initials: D
authors.lastname: Agrafiotis
authors.forename: B
authors.initials: B
authors.lastname: Caprathe
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: M R
authors.initials: MR
authors.lastname: Dickerson
authors.forename: J H
authors.initials: JH
authors.lastname: Fergus
authors.forename: T W
authors.initials: TW
authors.lastname: Hepburn
authors.forename: J S
authors.initials: JS
authors.lastname: Marks
authors.forename: M
authors.initials: M
authors.lastname: Van Dorf
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D016716:PC12 Cells; D011485:Protein Binding / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D009414:Nerve Growth Factors; C096822:PD 90780; D011799:Quinazolines; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins