Samuel Banister is cofounder and Chief Scientific Officer at Xylo Bio; a biotech start-up focused on the development of next-generation psychedelic-inspired medicines. Sam has been developing new therapeutics in the fields of psychiatry and neurology for more than 15 years at leading academic institutions (Stanford University, University of Sydney, UNSW) and biotech start-ups (Tranquis Therapeutics, Nalu Bio, Pangea Botanica). Prior to cofounding Xylo Bio, he was Team Leader in Medicinal Chemistry at The Lambert Initiative for Cannabinoid Therapeutics, and before that was a postdoc at Stanford University developing PET tracers for neuroinflammation, exploring new therapeutic targets for neurodegeneration, and profiling new psychoactive substances (NPS).

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Novel 5-MeO-DMT analogues with anxiolytic activity

5-MeO-DMT is a naturally occurring psychedelic under clinical investigation for the treatment of mood disorders and substance use disorders. We have synthesized a systematic library of ring-substituted analogues of 5-MeO-DMT featuring various N,N-dialkyl substitution patterns.  Like 5-MeO-DMT, all analogues demonstrated potent, efficacious activation of 5-HT2A and 5-HT2C receptors. 5-MeO-DMT analogues with an additional substituent at the 4-position retained potent agonist activity at 5-HT1A, while substitutions at the 6- and 7-positions reduced or abolished 5-HT1A activity. Representative N-methyl-N-ethyl examples featuring a common ring-substituent at the 4-, 6-, and 7-positions were evaluated in the head-twitch response assay in mice, and showed dose-dependent 5-MeO-DMT-like profiles. Additionally, these analogues dose-dependently reduced immobility time in mice in an acute stress-modified tail suspension test, suggesting potential anxiolytic profile. Full details of the synthesis, receptor profiling, and behavioral evaluation of this systematic library of 5-MeO-DMT analogues will be presented.