E-6837

E-6837 is a selective, orally active ligand for the 5-HT6 receptor. It acts as a partial agonist on the presumed silent rat 5-HT6 receptor by monitoring the cAMP signaling pathway, while demonstrating full agonist activity on the constitutively activated human 5-HT6 receptor. E-6837 reduces food intake, decreases fat mass and body weight, and improves blood glucose control. This compound is relevant for research studies related to obesity.

5-HT6 receptor (human):9.13 (pKi)

E-6837 selectively binds with high affinity to recombinant human 5-HT6 receptors in HEK-293 cell membrane preparations (pK i = 9.13 ± 0.17). It acts as a potent partial agonist (E max = 67 ± 4%, pEC 50 = 9.19 ± 0.11) and partial antagonist (I max = 41 ± 3%, pIC 50 = 8.37 ± 0.09) on the presumptive silent rat 5-HT6 receptors stably expressed in HEK-293F cells. Moreover, E-6837 functions as a highly potent near-full agonist (E max = 96 ± 4%, pEC 50 = 9.53 ± 0.09) on constitutively active human 5-HT6 receptors also stably expressed in HEK-293F cells.

E-6837 administered orally at doses of 5-30 mg/kg exhibits distinct effects in rodent models. A single dose of 30 mg/kg in male Sprague-Dawley rats causes a transient suppression of food intake lasting up to 6 hours, while a 5 mg/kg dose shows no impact on feeding behavior. At a dose of 60 mg/kg (oral, single dose), E-6837 does not induce conditioned taste aversion or kaolin consumption in male Sprague-Dawley rats, indicating no emetic or aversive effects at this level. Furthermore, a regimen of 30 mg/kg administered twice daily over 28 consecutive days leads to a maximum weight reduction of 15.7% in diet-induced obese female Wistar rats.