ENX-105

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]

ENX-105

Clinical data
Other names	ENX105; Deuterated nemonapride enantiomer[1]
Identifiers
IUPAC name 5-chloro-2-methoxy-N-((2R,3R)-2-methyl-1-(phenylmethyl-d2)pyrrolidin-3-yl)-4-((methyl-d3)amino)benzamide
CAS Number	2950168-16-6
PubChem CID	172553460
Chemical and physical data
Formula	C21H21ClD5N3O2
Molar mass	392.94 g·mol−1
3D model (JSmol)	Interactive image
SMILES 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 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

The drug is described as a dopamine D₂ and D₃ receptor antagonist and serotonin 5-HT_1A and 5-HT_2A receptor agonist.^[2][1][4] Its antagonistic potencies (IC₅₀Tooltip half-maximal inhibitory concentration) are 0.08 nM at the dopamine D_2L receptor, 0.8 nM at the dopamine D_2S receptor, and 3.8 nM at the dopamine D₃ receptor, whereas its activational potencies (EC₅₀Tooltip half-maximal effective concentration) are 5 nM at the serotonin 5-HT_2A receptor and 16 nM at the serotonin 5-HT_1A 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]