5-HT₆ Receptor Ligand

5-HT1AR/5-HT6R ligand-1 (Compound PP13) is the ligand for 5-HT receptor that exhibits good affinity to 5-HT1AR, 5-HT6R and 5-HT7R (K_i of 19, 69 and 198 nM, respectively), thereby inhibiting the cAMP production in HEK293 cell with EC₅₀ of 1535, 488 and 53 nM, respectively. 5-HT1AR/5-HT6R ligand-1 exhibits anti-proliferative activity against a variety of cancer cells (IC₅₀ for 1321N1, U87MG, MCF7, and AsPC-1 is 9.6, 13.6, 19.3 and 14.6 μM, respectively). 5-HT1AR/5-HT6R ligand-1 also exhibits antagonist activity for dopamine receptor D2R with K_i of 1903 nM.

PZ-1129 is a selective 5-HT7 receptor ligand with a K_i of 7 nM. PZ-1129 shows K_i values of 159 and 24 nM for 5-HT1A receptor and D2 receptor. PZ-1129 can inhibit the constitutive cAMP production mediated by the Gs signaling pathway (EC₅₀ = 13.7 nM). PZ-1129 can be used for the research of emotional disorders, such as depression and bipolar disorder.

5-HT5AR/5-HT6R ligand-1 (Compound PP10) is a ligand for serotonin receptors, showing high affinity for 5-HT_5A and 5-HT₆ receptors, with K_i values of 59 nM and 96 nM, respectively. 5-HT5AR/5-HT6R ligand-1 exhibits certain antiproliferative activity against tumor cells and can be used in the study of cancer.

E-6837 is a selective and orally active 5-HT₆ receptor ligand. E-6837 demonstrates partial agonism at a presumably silent rat 5-HT₆ receptor and full agonism at a constitutively active human 5-HT₆ receptor by monitoring the cAMP signaling pathway. E-6837 induces hypophagia, reduces fat mass and body weight, and improves glycemic control. E-6837 can be used for the research of obesity.