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GM-3009

From Wikipedia, the free encyclopedia

GM-3009
Clinical data
Other namesGM3009
Routes of
administration
Unspecified[1]
Drug classκ-Opioid receptor agonist

GM-3009 is a κ-opioid receptor (KOR) agonist and noribogaine analogue which is under development for the treatment of opioid-related disorders.[1][2][3] Its route of administration is unspecified.[1]

The drug is a highly potent agonist of the human KOR, with an affinity (Ki) of 0.9 nM or 87.3 nM depending on the radioligand and an EC50Tooltip half-maximal effective concentration of 0.8 nM.[3] In contrast to noribogaine, it did not show pro-arrhythmic effects in fresh human ventricular cardiomyocytes ex vivo.[3] GM-3009 produces antinociceptive effects and dose-dependently reduces oxycodone self-administration in rodents.[3]

It is being developed by Gilgamesh Pharmaceuticals.[1][2] As of June 2024, it is in the preclinical research stage of development.[1][2] The exact chemical structure of GM-3009 does not yet appear to have been disclosed.[1] However, it is known to be an "oxa-iboga" derivative.[4] Oxa-ibogaine analogues have notably been patented and studied by Dalibor Sames and colleagues, with Sames being a co-founder of Gilgamesh Pharmaceuticals.[5][6][7]

See also

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References

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  1. 1 2 3 4 5 6 "GM 3009". AdisInsight. 19 June 2024. Retrieved 16 February 2025.
  2. 1 2 3 "Delving into the Latest Updates on GM-3009 with Synapse". Synapse. 23 January 2025. Retrieved 16 February 2025.
  3. 1 2 3 4 Cunningham M, Nicholson K, Hughes Z, Sames D, Kruegel A (2023). "ACNP 62nd Annual Meeting: Poster Abstracts P501 – P753: P720. GM-3009 is a Novel Noribogaine Analog That Disrupts Opioid Self-Administration in Rats Via Agonism of Kappa Opioid Receptors Without Pro-Arrhythmic Effects on Human Cardiomyocytes" (PDF). Neuropsychopharmacology. 48 (S1): 355–495 (478–478). doi:10.1038/s41386-023-01757-3. ISSN 0893-133X. PMC 10729598. PMID 38040811. Retrieved 16 February 2025.
  4. Gerard Joseph Marek (2024). "Development of a Safer and More Effective Ibogaine Analog for the Treatment of Opioid Use Disorder". RePORT ⟩ RePORTER. Retrieved 6 April 2026. To leverage ibogaine's potential as an OUD therapeutic and address the risks to patient safety, we have developed a new class of synthetic iboga alkaloids, named "oxa-iboga". These compounds show no pro-arrhythmic potential, no neurotoxic effects, and enhanced efficacy in OUD-relevant preclinical behavioral assays compared to ibogaine. We propose to advance one of these compounds, GM-3009, into clinical studies by advancing GMP-manufacturing and formulation of GM-3009, completing IND-enabling toxicity studies, and determining the expected therapeutic exposures of GM-3009 and target engagement via translational biomarkers.
  5. "Oxa-ibogaine analogues for treatment of substance use disorders". Google Patents. 17 February 2022. Retrieved 6 April 2026.
  6. "Oxa-ibogaine inspired analogues for treatment of neurological and psychiatric disorders". Google Patents. 7 August 2023. Retrieved 6 April 2026.
  7. Havel V, Kruegel AC, Bechand B, McIntosh S, Stallings L, Hodges A, et al. (September 2024). "Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models". Nat Commun. 15 (1): 8118. doi:10.1038/s41467-024-51856-y. PMC 11415492. PMID 39304653.