Tasimelteon: a selective and unique receptor binding profile

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 MT 1 and MT 2 , 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 MT 2 receptor believed to mediate circadian rhythm phase-shifting (K i = 0.0692 nM and K i = 0.17 nM in NIH-3T3 and CHO–K1 cells, respectively), than for the MT 1 receptor (K i = 0.304 nM and K i = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.