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KB-128
Clinical data
Other namesKB128
Routes of
administration		Unspecified[1]
Drug classSerotonin 5-HT2C receptor agonist; Serotonin 5-HT2A receptor antagonist; Serotonin 5-HT2B receptor antagonist

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

[edit]

References

[edit]
  1. ^ a b c d e f g h i "KB 128". AdisInsight. 4 November 2025. Retrieved 24 March 2026.
  2. ^ a b c d e f g "Delving into the Latest Updates on KB-128 with Synapse". Synapse. 16 July 2025. Retrieved 24 March 2026.
  3. ^ a b c "Psychedelic Drug Development Tracker". Psychedelic Alpha. Retrieved 24 March 2026.
  4. ^ a b c d e f Jeremy Forest. "Novel and functionally selective 5-HT2C receptor agonist for treating Alcohol Use Disorder". RePORTER. Retrieved 24 March 2026. 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. ^ a b c d e "Küleon announces trifunctional serotonergic small molecule for neuropsychiatric disorders". BioWorld. 24 March 2026. Retrieved 24 March 2026. 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. ^ a b c d e f "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". BioSpace. 5 October 2023. Retrieved 24 March 2026.
  7. ^ a b "Küleon Bioscience Awarded $2 Million NIAAA Grant to Advance a Novel, Non-Hallucinogenic 5-HT2C Therapeutic Program for Alcohol Use Disorder". firstwordpharma.com. 23 September 2025. Retrieved 24 March 2026.
  8. ^ Kathryn Cunningham (2024). "Investigation of KB-128 on Methamphetamine-Induced Hyperactivity". UTMB Health Research Expert Profiles. Retrieved 24 March 2026.
  9. ^ a b "Benzoselenophene, benzothiophene, and benzofuran analogs and methods of modulating the serotonin 5-HT2C receptor". Google Patents. 25 April 2023. Retrieved 24 March 2026.
  10. ^ "Hallucinogenic and non-hallucinogenic serotonin receptor agonists and methods of making and using the same". Google Patents. 11 August 2022. Retrieved 8 April 2026.
  11. ^ "Hallucinogenic and non-hallucinogenic compounds and methods of making and using the same". Google Patents. 19 August 2022. Retrieved 8 April 2026.
  12. ^ "Serotonin receptor agonists and methods of making and using the same". Google Patents. 3 October 2022. Retrieved 8 April 2026.
5-HT1
5-HT1A
  • Positive allosteric modulators: Oleamide
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
  • Negative allosteric modulators: Oleamide
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