A new small-molecule antagonist inhibits Graves' disease antibody activation of the TSH receptor.

ABSTRACT:

Context

Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD.

Objective

Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon.

Design

We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing

SUBMITTER: Neumann S 

PROVIDER: S-EPMC3048317 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature