ENX-105

Last updated
ENX-105
ENX-105.svg
Clinical data
Other namesENX105; Deuterated nemonapride enantiomer [1]
Identifiers
  • 5-chloro-2-methoxy-N-((2R,3R)-2-methyl-1-(phenylmethyl-d2)pyrrolidin-3-yl)-4-((methyl-d3)amino)benzamide
CAS Number
PubChem CID
Chemical and physical data
Formula C21H21ClD5N3O2
Molar mass 392.94 g·mol−1
3D model (JSmol)
  • C(N[C@H]1[C@@H](C)N(C(C2=CC=CC=C2)([2H])[2H])CC1)(=O)C3=C(OC)C=C(NC([2H])([2H])[2H])C(Cl)=C3
  • InChI=1S/C21H26ClN3O2/c1-14-18(9-10-25(14)13-15-7-5-4-6-8-15)24-21(26)16-11-17(22)19(23-2)12-20(16)27-3/h4-8,11-12,14,18,23H,9-10,13H2,1-3H3,(H,24,26)/t14-,18-/m1/s1/i2D3,13D2
  • Key:KRVOJOCLBAAKSJ-RUFGIDIBSA-N

ENX-105 is an investigational new drug being developed by Engrail Therapeutics for the treatment of post-traumatic stress disorder (PTSD). [2] [3] [4] [5] It is currently in the preclinical stage, trailing behind a closely related Engrail compound, ENX-104, [1] which is focused on depression and anhedonia. [3]

The drug is described as a dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist. [2] [1] [4] Its antagonistic potencies (IC50 Tooltip half-maximal inhibitory concentration) are 0.08 nM at the dopamine D2L receptor, 0.8 nM at the dopamine D2S receptor, and 3.8 nM at the dopamine D3 receptor, whereas its activational potencies (EC50 Tooltip half-maximal effective concentration) are 5 nM at the serotonin 5-HT2A receptor and 16 nM at the serotonin 5-HT1A receptor. [2]

ENX-105 does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence is putatively non-hallucinogenic. [2] [1] The drug has shown anxiolytic-, antipsychotic-, anti-anhedonic-, and pro-cognitive-like effects in rodents. [2] It has also been found to increase dopamine levels in the nucleus accumbens in rodents. [2]

As with ENX-104, ENX-105 is a deuterated enantiomer of nemonapride. [1]

References

  1. 1 2 3 4 5 "Corporate Summary" (PDF). Engrail Therapeutics, Inc. 2024.
  2. 1 2 3 4 5 6 Vadodaria KC, Kangas BD, Serrats J, Brubaker W, Pizzagalli DA, Sudarsan V, Vanover KE (December 2024). "ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P698. A Novel Class of Non-Hallucinogenic Neuroplastogens with a Unique Combination of Serotonin 5-HT1A/2A Receptor Agonism and Dopamine D2/3 Receptor Antagonism". Neuropsychopharmacology. 49 (Suppl 1): 418–594 (470–470). doi: 10.1038/s41386-024-02013-y . PMID   39643635.
  3. 1 2 Bayer M (19 March 2024). "Engrail closes $157M series B, fueled by investors' renewed interest in neuropsychiatry". Fierce Biotech.
  4. 1 2 "ENX-105". PatSnap.
  5. ↑ WO 2023130117,Vadodaria K, Vanover K, Serrats J, Sudarsan V, Garvey D,"Preparation of deuterated pyrrolidin derivatives as modulators of dopamine and serotonin neurotransmission useful in treatment of diseases", assigned to Engrail Therapeutics, Inc.


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