Thyronamines and analogues - Translational research on thyronergic amines – The route from rediscovery of thyronamines to the bedside

Publication date: Available online 6 January 2017
Source:Molecular and Cellular Endocrinology
Author(s): Grazia Chiellini, Lorenza Bellusci, Martina Sabatini, Riccardo Zucchi
Thyronamines are a novel class of endogenous signaling compounds, structurally related to thyroid hormones (THs). Specific thyronamines, particularly 3-iodothyronamine (T1AM), stimulate with nanomolar affinity trace amine-associated receptor 1 (TAAR1), a G protein-coupled membrane receptor, and may also interact with other TAAR subtypes (particularly TAAR5), adrenergic receptors (particularly α2 receptors), amine transporters, and mitochondrial proteins. In addition to its structural similarities with THs, T1AM also contains the arylethylamine scaffold as in monoamine neurotransmitters, implicating an intriguing role for T1AM as both a neuromodulator and a hormone-like molecule constituting a part of thyroid hormone signaling. A large number of T1AM derivatives have already been synthesized. We discuss the different chemical strategies followed to obtain thyronamine analogues, their potency at TAAR1, and their structure-activity relationship. Preliminary characterization of the functional effects of these synthetic compounds is also provided.

Graphical abstract

http://ift.tt/2iLhCR6