Chemistry:KB-128

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KB-128 is a serotonin 5-HT2 receptor modulator which is under development for the treatment of alcoholism (alcohol use disorder).[1][2][3][4][5] Its route is unspecified.[1]

The drug acts as a biased agonist of the serotonin 5-HT2C receptor, with high Gq protein bias and minimal or negligible β-arrestin recruitment.[4][1][2][5][6] It additionally acts as a silent antagonist of the serotonin 5-HT2A and 5-HT2B receptors.[4][1][2][5][6] Due to its lack of activation of the serotonin 5-HT2A and 5-HT2B receptors, KB-128 is expected to lack hallucinogenic activity and cardiac valvulopathy risk, respectively.[4][5][6] The drug has been reported to reduce alcohol consumption in rodents.[4][7] It is being studied in terms of influence on methamphetamine-induced hyperactivity in rodents as well.[8]

KB-128 is under development by Küleon Bioscience (formerly Psilosterics).[1][2][3] It was first described by 2023.[1][2][6] As of November 2025, the drug is in the preclinical research stage of development for treatment of alcoholism.[1][2] There is also interest in KB-128 for potential treatment of various other conditions, including schizophrenia, Alzheimer's disease psychosis, depression, other addictions like stimulant use disorder, and obesity.[5][6][2] KB-128 is listed on Psychedelic Alpha's drug development tracker and hence may be related to serotonergic psychedelics.[3] The chemical structure of KB-128 does not yet appear to have been disclosed,[1] though KB-128's structure is known to have been patented.[4][9]

Besides KB-128, other candidates of Küleon Bioscience in earlier development include selective serotonin 5-HT2A receptor agonists and mixed serotonin 5-HT2A and 5-HT2C receptor agonists, for instance non-hallucinogenic psychoplastogens.[6][7] They have also patented many additional hallucinogenic and non-hallucinogenic compounds besides KB-128.[9][10][11][12]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "KB 128". 4 November 2025. https://adisinsight.springer.com/drugs/800084656. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Delving into the Latest Updates on KB-128 with Synapse". 16 July 2025. https://synapse.patsnap.com/drug/2fc4bb90ecc04adbb12e4337ec1d13e9. 
  3. ↑ 3.0 3.1 3.2 "Psychedelic Drug Development Tracker". https://psychedelicalpha.com/resources/psychedelic-drug-development-tracker/. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Novel and functionally selective 5-HT2C receptor agonist for treating Alcohol Use Disorder". https://reporter.nih.gov/project-details/11061454. "Our preliminary studies demonstrate lead candidate KB128 exhibits high selectivity for 5-HT2C, Gq-mediated signaling bias with minimal β-arrestin recruitment, favorable metabolic profile, no hallucinogenic or cardiotoxic liabilities, and efficacy in a pilot AUD study in rodents. [...] KB128 represents a novel class of molecules that we have developed and patented (US Patent No. 11,780,807); it is unique among drugs that target the same receptor because it exhibits functionally selective signaling within the cell, while exhibiting an antagonistic (blocking) effect at the 5-HT2A and 5-HT2B receptors." 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "Küleon announces trifunctional serotonergic small molecule for neuropsychiatric disorders". 24 March 2026. https://www.bioworld.com/articles/701613-kuleon-announces-trifunctional-serotonergic-small-molecule-for-neuropsychiatric-disorders?v=preview. "Küleon LLC (formerly Psilosterics LLC) has announced a trifunctional serotonergic small molecule that is a full 5-HT2C receptor agonist and full antagonist of the 5-HT2A and 5-HT2B receptors with potential to treat neuropsychiatric disorders. Designated KB-128, it could be developed to treat disorders that can be modulated though 5-HT2C receptors, including schizophrenia, Alzheimer’s psychosis, depression, obesity and addiction." 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "Küleon Bioscience Announces Scientific Breakthrough with First Known Trifunctional 5-HT2C Receptor Agonist that is also a Full Antagonist of the 5-HT2A and 5-HT2B Receptors, Creating an Exciting Lead for Multiple Neuropsychiatric Illnesses". 5 October 2023. https://www.biospace.com/kueleon-bioscience-announces-scientific-breakthrough-with-first-known-trifunctional-5-ht2c-receptor-agonist-that-is-also-a-full-antagonist-of-the-5-ht2a-and-5-ht2b-receptors-creating-an-exciting-lead-for-multiple-neuropsychiatric-illnesses. 
  7. ↑ 7.0 7.1 "Küleon Bioscience Awarded $2 Million NIAAA Grant to Advance a Novel, Non-Hallucinogenic 5-HT2C Therapeutic Program for Alcohol Use Disorder". 23 September 2025. https://firstwordpharma.com/story/6095224. 
  8. ↑ "Investigation of KB-128 on Methamphetamine-Induced Hyperactivity". 2024. https://researchexperts.utmb.edu/en/projects/investigation-of-kb-128-on-methamphetamine-induced-hyperactivity-2/. 
  9. ↑ 9.0 9.1 Gilles D, "Benzoselenophene, benzothiophene, and benzofuran analogs and methods of modulating the serotonin 5-HT2C receptor", US patent 11780807
  10. ↑ Gilles D, "Hallucinogenic and non-hallucinogenic serotonin receptor agonists and methods of making and using the same", WO patent 2023018864
  11. ↑ Gilles D, "Hallucinogenic and non-hallucinogenic compounds and methods of making and using the same", WO patent 2023023298
  12. ↑ Gilles D, "Serotonin receptor agonists and methods of making and using the same", WO patent 2023059546



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