Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity

Kaplan, A. L. et al. Nature 610, 582–591 (2022).

Researchers computationally screened a bespoke virtual library of 75 million tetrahydropyridine-containing compounds against the serotonin 5-HT2A receptor.

REPORTED FINDINGS

01Selected molecules were synthesized and experimentally evaluated.

02Two candidates produced antidepressant-like behavioral effects in mice without the standard mouse head-twitch proxy.

03The work demonstrates a receptor-informed computational discovery pipeline.

LIMITS / CAUTION

Mouse behavioral proxies do not establish antidepressant efficacy, subjective effects, or safety in humans.