New small molecule agonists to the thyrotropin receptor.

ABSTRACT:

Background

Novel small molecular ligands (SMLs) to the thyrotropin receptor (TSHR) have potential as improved molecular probes and as therapeutic agents for the treatment of thyroid dysfunction and thyroid cancer.

Methods

To identify novel SMLs to the TSHR, we developed a transcription-based luciferase-cAMP high-throughput screening system and we screened 48,224 compounds from a 100K library in duplicate.

Results

We obtained 62 hits using the cut-off criteria of the mean±three standard deviations above the baseline. Twenty molecules with the greatest activity were rescreened against the parent CHO-luciferase cell for nonspecific activation, and we selected two molecules (MS437 and MS438) with the highest potency for further study. These lead molecules demonstrated no

SUBMITTER: Latif R 

PROVIDER: S-EPMC4291085 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature