The Next Generation of Serotonergic Drugs

Our Approach

Functional Selectivity

Our primary lead compounds are novel small molecule therapeutics that are 5-HT2C receptor agonists that exhibit a full antagonistic (blocking) effect at 5-HT2A and 5-HT2B receptors. Even minimal activation of 5-HT2A and 5-HT2B is associated with significant adverse effects, including psychiatric (insomnia and hallucinations) and cardiotoxic (valvular heart disease and pulmonary arterial hypertension) liabilities. Our pilot in vitro and in vivo studies also demonstrate that our lead compounds modulate 5-HT2C via a Gq-mediated signaling bias with minimal β-arrestin recruitment, resulting in “functional selectivity” for 5-HT2C. Thus, Küleon has developed what is believed to be the world’s first functionally selective 5-HT2C receptor agonist that is a full antagonist of the 5-HT2A and 5-HT2B receptors. We also apply this functional selective approach to our other lead programs (see Lead Programs).