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CYB003
Clinical data
Other namesCYB-003; deuterated psilocybin analogue; deuterated psilocin analogue
Routes of
administration		By mouth[1]
Drug classSerotonergic psychedelic[1][2]
ATC code
  • None
Pharmacokinetic data
Onset of action30 minutes (Cmax) (rats)[3]
Elimination half-life45 minutes (rats)[3]

CYB003, or CYB-003, also known as deuterated psilocybin analogue, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders.[1][4][5][6][7][2][3] It is taken by mouth.[1]

It is a tryptamine derivative and is a deuterated analogue of psilocybin and psilocin.[1][5][6][2] The pharmacodynamic profile of CYB003, including its interactions with serotonin receptors and its effects in animals, is similar to that of psilocin.[2] As with psilocin, CYB003 is a potent agonist of the serotonin 5-HT2A receptor and produces psychedelic-like effects in animals.[2] However, it was developed to have improved pharmacokinetic properties compared to psilocybin, including reduced variability in circulating levels, a faster onset of action, and a shorter duration.[3]

As of October 2024, CYB003 is in phase 3 clinical trials for major depressive disorder and is in the preclinical stage of development for alcoholism and other psychiatric disorders.[1][4] Two phase 3 clinical trials for major depressive disorder are being initiated in November 2024 and February 2025.[1][4] The drug is under development by Cybin.[1][4] The chemical structure of CYB003 has not yet been disclosed.[6][5] However, Cybin patented deuterated tryptamines including the dideuterated psilocin analogue PI-α,α-d2 (psilocin dideuterated at the α carbon) in 2023.[8] Other related drugs include the deuterated tryptamine CYB004, the deuterated phenethylamine CYB005, and the phenethylamine CYB210010.[5][9]

An INNTooltip International Nonproprietary Name of deupsilocin for a deuterated form of psilocin called d10-psilocin with CAS number 1435934-64-7 was proposed in 2023 and recommended in 2024.[10][11][12] This deuterated analogue of psilocin was patented in 2021 by Lennham Pharmaceuticals.[12] It is said to be in phase 3 trials.[13]

See also

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References

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  1. ^ a b c d e f g h "CYB 003". AdisInsight. 4 October 2024. Retrieved 23 October 2024.
  2. ^ a b c d e Palfreyman M, Krakowsky J, Morgan M, Canal C, Pathare P, Avery K, et al. (December 2022). "ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P361. In Vitro and In Vivo Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder" (PDF). Neuropsychopharmacology. 47 (Suppl 1): 220–370 (271). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.
  3. ^ a b c d Inamdar A, Morgan M, Krakowsky J, Reichelt A, Canal C, Mueller T, et al. (December 2022). "ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P362. Pharmacokinetic Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder" (PDF). Neuropsychopharmacology. 47 (Suppl 1): 220–370 (271–272). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.
  4. ^ a b c d "Delving into the Latest Updates on CYB-003 with Synapse". Synapse. 12 October 2024. Retrieved 23 October 2024.
  5. ^ a b c d Cano GH, Dean J, Abreu SP, Rodríguez AH, Abbasi C, Hinson M, et al. (December 2022). "Key Characteristics and Development of Psychoceuticals: A Review". Int J Mol Sci. 23 (24): 15777. doi:10.3390/ijms232415777. PMC 9779201. PMID 36555419.
  6. ^ a b c Di Martino RM, Maxwell BD, Pirali T (July 2023). "Deuterium in drug discovery: progress, opportunities and challenges". Nat Rev Drug Discov. 22 (7): 562–584. doi:10.1038/s41573-023-00703-8. PMC 10241557. PMID 37277503.
  7. ^ Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST (December 2023). "Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders". Drug Discov Today. 28 (12): 103818. doi:10.1016/j.drudis.2023.103818. PMID 37925136.
  8. ^ "Deuterated tryptamine derivatives and methods of use". Google Patents. 17 July 2023. Retrieved 23 October 2024. Binding affinity (Ki) and functional potency (EC50) values of PI and PI-α-d2 are summarized in Table 1. Deuteration was found to have little effect on the affinity and function at key receptor targets. [...] TABLE 1: PI and PI-α,α-d2 Affinities and Functions at Target Serotonin Receptors [...]
  9. ^ Peplow M (June 2024). "Next-generation psychedelics: should new agents skip the trip?". Nat Biotechnol. 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. PMID 38831049.
  10. ^ deupsilocinum deupsilocin 3-[2-{di[(2H3)methyl]amino}(2H4)ethyl]-1H-indol-4-ol psychodysleptic [...] C12H62H10N2O 1435934-64-7 https://www.who.int/docs/default-source/international-nonproprietary-names-(inn)/pl129.pdf#page=35
  11. ^ deupsilocinum deupsilocin 3-[2-{di[(2H3)methyl]amino}(2H4)ethyl]-1H-indol-4-ol [...] C12H62H10N2O https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-%28inn%29/rl91.pdf
  12. ^ a b US 11000534, Bradford Sippy, "Deuterated Derivatives of Psilocybin and Uses Thereof", published 11 May 2021, issued 11 May 2021, assigned to Lennham Pharmaceuticals, Inc. 
  13. ^ Chen J, Zhu YY, Huang L, Zhang SS, Gu SX (April 2025). "Application of deuterium in research and development of drugs". Eur J Med Chem. 287: 117371. doi:10.1016/j.ejmech.2025.117371. PMID 39952095. Moreover, several deuterated compounds have entered Phase III clinical trials, including deupirfenidone, deupsilocin, deutenzalutamide, AVP-786, ALK-001, RT001 and Jaktinib, and numerous deuterated drugs are in phase I and II clinical studies.
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