title: Tasimelteon: a selective and unique receptor binding profile.
abstract: Hetlioz(®) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.
authors.affiliation: Vanda Pharmaceuticals Inc., 2200 Pennsylvania Ave. N.W., Suite 300-E, Washington, D.C, 20037, USA. Electronic address: Christian.lavedan@vandapharma.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Lavedan
authors.affiliation: Vanda Pharmaceuticals Inc., 2200 Pennsylvania Ave. N.W., Suite 300-E, Washington, D.C, 20037, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Forsberg
authors.affiliation: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, 06492, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gentile
mesh_terms: D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism*; D003521:Cyclopropanes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D044094:Receptors, Melatonin / Q000819:agonists* / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D003521:Cyclopropanes; D044094:Receptors, Melatonin; C478745:tasimelteon
keywords: Circadian regulator; Circadian rhythm; Hetlioz(®); Melatonin receptor; Non-24; Tasimelteon; Tasimelteon (PubChem CID:10220503)