c-Erb-A β-1 Inhibitors

The chemical class of c-Erb-A β-1 inhibitors encompasses a variety of compounds that inhibit the function of the thyroid hormone receptor beta-1 (THRβ1). These inhibitors can directly compete with thyroid hormones for receptor binding or modulate receptor activity, gene expression, and hormone synthesis. Direct inhibitors like NH-3 and tetrac act by occupying the ligand-binding domain of THRβ1, preventing the association of thyroid hormones, which is necessary for receptor activation and downstream gene transcription. Compounds such as 1-850 are designed to selectively antagonize THRβ1, reducing its transcriptional activity.

Some compounds may act as selective modulators, such as GC-1, which can also function as an antagonist under certain circumstances by inhibiting coactivator recruitment to THRβ1. Amiodarone, due to its structural similarity to thyroxine (T4), can interfere with thyroid hormone action, impacting THRβ1 function. Other inhibitors indirectly decrease THRβ1 activation by lowering thyroid hormone levels. MMI and PTU are antithyroid drugs that inhibit the synthesis of thyroid hormones, while ketoconazole affects hormone metabolism. Dexamethasone influences receptor expression, altering THRβ1's transcriptional activity.