Z3517967757 Explained

Z3517967757 (Z7757) is a piperidine derivative which acts as an agonist at the 5-HT₂ family of serotonin receptors, first reported in 2024. It has strongest activity at 5-HT_2A and lower affinity at the 5-HT_2B and 5-HT_2C subtypes. It was developed using in silico modelling to dock a large library of compounds against a 5-HT_2A receptor model generated by the artificial intelligence program AlphaFold, and then synthesised and tested in the laboratory to confirm activity. It has two stereogenic centers and four possible isomers, but has only been tested as a racemic mixture.^{[1] [2] [3]}

See also

• AAZ-A-154
• IHCH-7079
• IHCH-7086
• IHCH-7113
• (R)-69
• List of miscellaneous 5HT2A agonists

Notes and References

1. Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, Barros-Álvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Tummino TA, Huang S, Irwin JJ, Tarkhanova OO, Moroz Y, Skiniotis G, Kruse AC, Shoichet BK, Roth BL . 6 . AlphaFold2 structures template ligand discovery . bioRxiv . December 2023 . 38187536 . 10769324 . 10.1101/2023.12.20.572662 .
2. Callaway E . AlphaFold found thousands of possible psychedelics. Will its predictions help drug discovery? . Nature News . 18 January 2024 . 10.1038/d41586-024-00130-8. 38238624 .
3. Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, Barros-Álvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Glenn IS, Tummino TA, Huang S, Irwin JJ, Tarkhanova OO, Moroz Y, Skiniotis G, Kruse AC, Shoichet BK, Roth BL . AlphaFold2 structures guide prospective ligand discovery . Science . New York, N.Y. . eadn6354 . May 2024 . 38753765 . 10.1126/science.adn6354 .