Delving into the Latest Updates on TPO mimics(GSK) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

TPO receptor

Action

modulators

Mechanism

TPO receptor modulators(Thrombopoietin receptor modulators)

Therapeutic Areas

Hemic and Lymphatic Diseases

Active Indication

Thrombocytopenia

Inactive Indication-

Originator Organization

GSK Plc

Active Organization

GSK Plc

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Shah, Rakhi ; Eppley, Daniel F. ; Luengo, Juan I. ; Erickson-Miller, Connie ; Stark, Kenneth C. ; Wiggall, Kenneth J. ; Huang, Yifang ; Keenan, Richard M. ; Tyree, Curtis ; Tian, Shin-Shay ; Zhang, Lily ; Price, Alan T. ; Shaw, Tony N. ; Duffy, Kevin J. ; Dillon, Susan B. ; Smith, Heather ; Delorme, Evelyne ; Hopson, Christopher B. ; Darcy, Michael G. ; Lamb, Peter ; Liu, Nannan ; Rosen, Jon ; Leong, Lynnette ; Giampa, Leslie ; Miller, Stephen G.

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.

100 Deals associated with TPO mimics(GSK)

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