biostudies-literatureSchapira MNIDDK NIH HHS7354-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC165879biostudies-literatureUnknown100(12)Treatment of hyperthyroidism, a common clinical condition that can have serious manifestations in the elderly, has remained essentially unchanged for >30 years. Directly antagonizing the effect of the thyroid hormone at the receptor level may be a significant improvement for the treatment of hyperthyroid patients. We built a computer model of the thyroid hormone receptor (TR) ligand-binding domain in its predicted antagonist-bound conformation and used a virtual screening algorithm to select 100 TR antagonist candidates out of a library of >250,000 compounds. We were able to obtain 75 of the compounds selected in silico and studied their ability to act as antagonists by using cultured cells that express TR. Fourteen of these compounds were found to antagonize the effect of T3 on TR with ICProceedings of the National Academy of Sciences of the United States of AmericaDiscovery of diverse thyroid hormone receptor antagonists by high-throughput docking.PMC165879R42 DK059041DK16636R01 DK016636R41 DK059041DK59041R56 DK016636Raaka BMDas SSchapira MFan LAbagyan RWilson SRSamuels HHTotrov MZhou ZfalseDiscovery of diverse thyroid hormone receptor antagonists by high-throughput docking.Treatment of hyperthyroidism, a common clinical condition that can have serious manifestations in the elderly, has remained essentially unchanged for >30 years. Directly antagonizing the effect of the thyroid hormone at the receptor level may be a significant improvement for the treatment of hyperthyroid patients. We built a computer model of the thyroid hormone receptor (TR) ligand-binding domain in its predicted antagonist-bound conformation and used a virtual screening algorithm to select 100 TR antagonist candidates out of a library of >250,000 compounds. We were able to obtain 75 of the compounds selected in silico and studied their ability to act as antagonists by using cultured cells that express TR. Fourteen of these compounds were found to antagonize the effect of T3 on TR with IC2003-01-01T00:00:00Z2003 Jun2026-03-16T16:41:58.152Z2025-05-31T22:56:47.296ZS-EPMC1658791277762710.1073/pnas.1131854100