RS130-180

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| image = RS130-180.svg

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| class = β-Arrestin-biased serotonin 5-HT_2A receptor agonist

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| PDB_ligand = A1AFX

| synonyms = RS-130-180; N-(2-Propargyloxy)-2,5-dimethoxy-4-(dimethylamino)phenethylamine

| IUPAC_name = 2,5-dimethoxy-N,N-dimethyl-4-(2-((2-(prop-2-yn-1-yloxy)benzyl)amino)ethyl)aniline

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| SMILES = C(OC)1=C(N(C)C)C=C(OC)C(CCN([H])CC2=C(OCC#C)C=CC=C2)=C1

| StdInChI = 1S/C22H28N2O3/c1-6-13-27-20-10-8-7-9-18(20)16-23-12-11-17-14-22(26-5)19(24(2)3)15-21(17)25-4/h1,7-10,14-15,23H,11-13,16H2,2-5H3

| StdInChIKey = NDHJMNFRHQYXKX-UHFFFAOYSA-N

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RS130-180, also known as N-(2-propargyloxy)-2,5-dimethoxy-4-(dimethylamino)phenethylamine, is a β-arrestin-biased serotonin 5-HT_2A receptor agonist of the NBOMe family.{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | pages = 2734 | date = March 2025 | pmid = 40108183 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 }}{{cite conference |date=2022-09-16 |title=Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias |url=https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37 |conference=University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat |quote=Here we present 8 new cryoEM structures covering all major compound classes for the 5HT2AR including a novel arrestin biased compound RS130-180. |vauthors=Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL}}{{cite web | vauthors = Ağacı E | title=Exploring Psychedelics: New Insights Into Therapeutic Mechanisms | website=The Pinnacle Gazette | date=22 March 2025 | url=https://evrimagaci.org/tpg/exploring-psychedelics-new-insights-into-therapeutic-mechanisms-276602 | access-date=22 March 2025 | quote=For instance, rs130-180, a non-hallucinogenic variant, was identified as a biased agonist with therapeutic implications.}} The phenyl ring has an N,N-dimethylamino substituent at the 4 position, the benzyl ring has a propynyloxy substituent at the 2 position.

The drug favors activation of β-arrestin over G_q. RS130-180 is said to be useful for in-vitro studies, but to have suboptimal pharmacokinetic properties for in-vivo use. The cryo-EM structures of the serotonin 5-HT_2A receptor with RS130-180, as well as with various serotonergic psychedelics, have been published by Bryan Roth and colleagues.

RS130-180 was first reported in 2022. It was derived from an earlier compound called ZINC000341335936, which was identified via in-silico screening of 1.6{{nbsp}}billion molecules for serotonin 5-HT_2A receptor agonism with AlphaFold2.{{cite journal | vauthors = 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 | title = AlphaFold2 structures guide prospective ligand discovery | journal = Science | volume = 384 | issue = 6702 | pages = eadn6354 | date = June 2024 | pmid = 38753765 | doi = 10.1126/science.adn6354 | pmc = 11253030 | pmc-embargo-date = June 21, 2025 | bibcode = 2024Sci...384n6354L | url = https://thealonlab.org/papers/science.adn6354.pdf }}