Apimostinel

Apimostinel (GATE-202, formerly NRX-1074) is an investigational antidepressant, acting as a novel and selective modulator of the NMDA receptor.^[1][2][3][4] It is currently under development for the acute treatment of major depressive disorder (MDD) by Syndeio Biosciences, and previously by Naurex and Allergan.^[5][6][7] As of February 2015, an intravenous formulation of apimostinel has completed a phase IIa clinical trial for MDD.^[5][8]

Other namesNRX-1074; AGN-241660; Threonyl-prolyl-2R-(2-benzyl)-prolyl-threonine amide

Routes of
administrationBy mouth

Drug classNMDA receptor modulator

Legal status

• US: Investigational New Drug

Quick facts Clinical data, Other names ...

Apimostinel

Clinical data
Other names	NRX-1074; AGN-241660; Threonyl-prolyl-2R-(2-benzyl)-prolyl-threonine amide
Routes of administration	By mouth
Drug class	NMDA receptor modulator
Legal status
Legal status	US: Investigational New Drug
Identifiers
IUPAC name (2R)-1-[(2S)-1-[(2S,3R)-2-Amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-2-benzylpyrrolidine-2-carboxamide
CAS Number	1421866-48-9
PubChem CID	71249967
ChemSpider	52085607
UNII	TTT1F11FZB
KEGG	D11299
ChEMBL	ChEMBL3545230
CompTox Dashboard (EPA)	DTXSID101031863
Chemical and physical data
Formula	C25H37N5O6
Molar mass	503.600 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@@]2(Cc3ccccc3)C(=O)N[C@@H]([C@@H](C)O)C(N)=O
InChI InChI=1S/C25H37N5O6/c1-15(31)19(26)23(35)29-12-6-10-18(29)22(34)30-13-7-11-25(30,14-17-8-4-3-5-9-17)24(36)28-20(16(2)32)21(27)33/h3-5,8-9,15-16,18-20,31-32H,6-7,10-14,26H2,1-2H3,(H2,27,33)(H,28,36)/t15-,16-,18+,19+,20+,25-/m1/s1 Key:DVBUEXCIEIAXPM-PJUQSVSOSA-N

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Similar to rapastinel (GLYX-13), its mechanism of action acts through a unique binding site on the NMDA receptor, independent of the glycine site, to modulate receptor activity and enhance NMDAR-mediated synaptic plasticity.^[9] However, apimostinel is 1000-fold more potent in vitro and is intended as an improved, follow-up drug to rapastinel.^[2][5] Similar to rapastinel, apimostinel is an amidated tetrapeptide, but has been structurally modified, via the addition of a benzyl group, to enhance its metabolic stability and pharmacokinetic profile. The drug has shown rapid and potent antidepressant effects in pre-clinical models of depression.^[5] In addition, similarly to rapastinel, it is well tolerated and lacks the hallucinosis-like psychotomimetic effects of NMDA receptor antagonists such as ketamine.^[5]