Fig. 3.

Combination of ANTAG3 and 1H7 additively inhibits GO-Ig stimulation. a ANTAG3 is a fully efficacious TSHR antagonist for M22-induced HA secretion in GOFs regardless of M22 concentration. Cultured GOFs were stimulated with 1 nM M22, which is a maximally effective dose, or the half-maximally effective dose (EC_med) of M22, and cotreated with increasing doses of the small molecule TSHR antagonist ANTAG3 for 4 days. Total HA secretion was measured in the culture media. Data represent the mean of two donor cell strains plotted as percent HA levels relative to the 1 nM M22 maximal response [11]. b Combination treatment with TSHR and IGF-1R antagonists on HA stimulation by purified GO-Igs efficiently inhibits TSHR/IGF-1R crosstalk. Cultured GOFs were stimulated with GO-Igs purified from the sera of 6 different donors in the absence (not shown) or presence of the half-maximally effective inhibitory concentration (IC₅₀) of the TSHR antagonist ANTAG3 or the IGF-1R-blocking antibody 1H7 or both. HA secretion was measured after 5 days. Inhibition with an IC₅₀ dose of each antagonist separately is not complete; however, the combination of both antagonists at IC₅₀ doses was additive [11].