title: Thyronamines and Analogues - The Route from Rediscovery to Translational Research on Thyronergic Amines.
abstract: 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.
authors.affiliation: Department of Pathology, University of Pisa, Italy. Electronic address: g.chiellini@bm.med.unipi.it.
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.affiliation: Department of Pathology, University of Pisa, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellusci
authors.affiliation: Department of Pathology, University of Pisa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Sabatini
authors.affiliation: Department of Pathology, University of Pisa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013970:Thyronines / Q000737:chemistry / Q000494:pharmacology; D057170:Translational Research, Biomedical; D000095383:Trace Amine-Associated Receptors
chemical_list: D000588:Amines; D043562:Receptors, G-Protein-Coupled; D013970:Thyronines; D000095383:Trace Amine-Associated Receptors; C487948:3-iodothyronamine; C004547:thyronamine
keywords: Adrenergic receptors; Thyronamine-like compounds; Thyronamines; Trace amine-associated receptors