| Literature DB >> 11606138 |
K J Duffy1, M G Darcy, E Delorme, S B Dillon, D F Eppley, C Erickson-Miller, L Giampa, C B Hopson, Y Huang, R M Keenan, P Lamb, L Leong, N Liu, S G Miller, A T Price, J Rosen, R Shah, T N Shaw, H Smith, K C Stark, S S Tian, C Tyree, K J Wiggall, L Zhang, J I Luengo.
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.Entities:
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Year: 2001 PMID： 11606138 DOI： 10.1021/jm010283l
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446