PD-90780, A NONPEPTIDE INHIBITOR OF NERVE GROWTH-FACTORS BINDING TO THE P75 NGF RECEPTOR

Nerve growth factor is a peptide that supports the survival and differ entiation of discrete neuronal populations in the peripheral and centr al nervous systems. NGF binds to both trkA, a tyrosine kinase receptor , and to the p75 nerve growth factor receptor, a protein lacking a con sensus signalling sequence. We have identified a substituted pyrazoloq uinazolinone, 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 compoun d may be useful in identifying the region(s) of nerve growth factor in volved in binding to the p75 receptor and in clarifying the role of p7 5 receptor in the actions of the neurotrophins. (C) 1995 Academic Pres s, Inc.