Document Report Card

ID: ALA1134668

Journal: J Med Chem

Title: Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.

Authors: Duffy KJ, Darcy MG, Delorme E, Dillon SB, Eppley DF, Erickson-Miller C, Giampa L, Hopson CB, Huang Y, Keenan RM, Lamb P, Leong L, Liu N, Miller SG, Price AT, Rosen J, Shah R, Shaw TN, Smith H, Stark KC, Tian SS, Tyree C, Wiggall KJ, Zhang L, Luengo JI.

Abstract: High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

CiteXplore: 11606138

DOI: 10.1021/jm010283l