TGF-8027

Overview

TGF-8027, or TGF-8-027, also known as N-[1-(2-hydroxyphenyl)ethyl]-2,5-dimethoxy-4-cyanophenethylamine, is a highly selective serotonin 5-HT2A receptor agonist and putative serotonergic psychedelic of the phenethylamine, 2C, and 25-NB (NBOH) families. It is one of the most selective serotonin 5-HT2A receptor agonists known and shows much greater selectivity than earlier agents like 25CN-NBOH, DMBMPP, and LPH-5. The drug produces psychedelic-like effects in rodents and hence may be hallucinogenic in humans. TGF-8027 was first described in the literature in 2025.[1] WP

Drug class

Selective serotonin 5-HT2A receptor agonist Serotonergic psychedelic Hallucinogen WP

From the Wikipedia article's infobox.

Pharmacology

Pharmacodynamics

TGF-8027 acts as a highly selective serotonin 5-HT2A receptor full agonist. Its affinities (Kᵢ) were 7.4 nM at the serotonin 5-HT2A receptor, 390 nM at the serotonin 5-HT2B receptor, and 1,100 nM at the serotonin 5-HT2C receptor. The drug's EC₅₀ (half-maximal effective concentration) and Eₘₐₓ (maximal efficacy) values in terms of Gq dissociation were 3.3 nM (91%) at the human serotonin 5-HT2A receptor, 7,600 nM (45%) at the human serotonin 5-HT2B receptor, and 160 nM (123%) at the human serotonin 5-HT2C receptor. It was also assessed at these receptors with other assays. In addition, TGF-8027 was screened at a large panel of other targets, including receptors and transporters, and showed relatively little affinity at these sites.[1] WP

With regard to selectivity for the human serotonin 5-HT2A receptor over the human serotonin 5-HT2C receptor, TGF-8027 showed 149-fold selectivity in terms of affinity, 48.5-fold selectivity in terms of Gq dissociation, 84.5-fold selectivity in terms of calcium flux, and 2,450-fold selectivity in terms of IP1 accumulation. It is far more selective as an agonist of the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor than previous selective serotonin 5-HT2A receptor agonists such as 25CN-NBOH, DMBMPP, and rac-LPH-5 (fold selectivity for Gq dissociation in the same study of 10.0, 13.5, and 4.4, respectively). Previous research had not rigorously assessed the selectivity of these earlier compounds via employment of multiple selectivity assays.[1] WP

TGF-8027 was less selective for the mouse serotonin 5-HT2A receptor over the mouse serotonin 5-HT2C receptor, but still showed about 15-fold selectivity for the former over the latter in terms of Gq dissociation. In accordance with its serotonin 5-HT2A receptor activation, the drug robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in mice. As such, it would be expected to produce psychedelic effects in humans.[1] WP

The compound is a racemic mixture of (+)- and (–)-enantiomers, with the (–)-enantiomer being a more potent serotonin 5-HT2A receptor agonist but the (+)-enantiomer being more selective for activation of the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor.[1] WP

History

History

TGF-8027 was first described in the scientific literature by John McCorvy's lab and colleagues in 2025. The group also included Adam Halberstadt. The serotonin 5-HT2A and 5-HT2C receptors show considerable homology, which has made development of selective serotonin 5-HT2A receptor agonists difficult. TGF-8027 was discovered via a rational structure-guided design that took advantage of an identified single-residue difference between the serotonin 5-HT2A receptor and the serotonin 5-HT2C receptor in transmembrane 2 (TM2) of the extended binding pocket. The group also reported a series of other selective serotonin 5-HT2A receptor agonists in addition to TGF-8027, some of which showed even further improved selectivity. TGF-8027 was selected for more in-depth characterization over other compounds, for instance in the head-twitch response assay, because it showed among the highest selectivity and potency at the mouse serotonin 5-HT2A receptor in addition to the human serotonin 5-HT2A receptor.[1] WP

Legal status

Canada

TGF-8027 may be a controlled substance in Canada under phenethylamine blanket-ban language.[2] WP

United states

TGF-8027 is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.[3] WP

Chemistry

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Fenske TG, McKee JL, Cavalco NG, Schalk SS, Bonniwell EM, Lammers JC, Shacham N, Cuccurazzu B, Halberstadt AL, McCorvy JD. Discovery of Highly Selective 5-HT2A Agonists Using Structure-Guided Design. J Med Chem. September 2025. doi:10.1021/acs.jmedchem.5c01855 · PMID 40997862
2. Other Controlled Drugs and Substances Act
3. Other Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026). January 2026

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