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Apimostinel

October 15, 2023

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 Gate Neurosciences, 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]

Apimostinel
Clinical data
Other namesNRX-1074; AGN-241660; Threonyl-prolyl-2R-(2-benzyl)-prolyl-threonine amide
Routes of
administration		By mouth
Legal status
Legal status
Identifiers
  • (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
Chemical and physical data
FormulaC25H37N5O6
Molar mass503.600 g·mol−1
3D model (JSmol)
  • Interactive image
  • 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=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

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 schizophrenia-like psychotomimetic effects of NMDA receptor antagonists such as ketamine.[5]

See also Edit

References Edit

  1. ^ "Naurex's Novel Antidepressant GLYX-13 Recognized as One of Windhover's Top 10 Neuroscience Projects to Watch". PR Newswire. 31 August 2010.
  2. ^ a b Henter ID, Park LT, Zarate CA (May 2021). "Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status". CNS Drugs. 35 (5): 527–543. doi:10.1007/s40263-021-00816-x. PMC 8201267. PMID 33904154.
  3. ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019). "Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects". The International Journal of Neuropsychopharmacology. 22 (3): 247–259. doi:10.1093/ijnp/pyy101. PMC 6403082. PMID 30544218.
  4. ^ Hayley S, Litteljohn D (November 2013). "Neuroplasticity and the next wave of antidepressant strategies". Frontiers in Cellular Neuroscience. 7: 218. doi:10.3389/fncel.2013.00218. PMC 3834236. PMID 24312008.
  5. ^ a b c d e . PR Newswire. 6 May 2014. Archived from the original on 14 July 2014.
  6. ^ "Allergan Successfully Completes Naurex Acquisition". Allergan plc (Press release). PR Newswire. Retrieved 2016-11-20.
  7. ^ "Home - Gate Neurosciences". Retrieved 2022-05-12.
  8. ^ Clinical trial number NCT02067793 for "Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder" at ClinicalTrials.gov
  9. ^ Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019). "Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects". The International Journal of Neuropsychopharmacology. 22 (3): 247–259. doi:10.1093/ijnp/pyy101. PMC 6403082. PMID 30544218.

External links Edit

  • Apimostinel (NRX-1074) - AdisInsight

October 15, 2023
apimostinel, gate, formerly, 1074, investigational, antidepressant, acting, novel, selective, modulator, nmda, receptor, currently, under, development, acute, treatment, major, depressive, disorder, gate, neurosciences, previously, naurex, allergan, february, . 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 Gate Neurosciences 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 ApimostinelClinical dataOther namesNRX 1074 AGN 241660 Threonyl prolyl 2R 2 benzyl prolyl threonine amideRoutes ofadministrationBy mouthLegal statusLegal statusUS Investigational New DrugIdentifiersIUPAC 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 carboxamideCAS Number1421866 48 9PubChem CID71249967ChemSpider52085607UNIITTT1F11FZBKEGGD11299ChEMBLChEMBL3545230Chemical and physical dataFormulaC 25H 37N 5O 6Molar mass503 600 g mol 13D model JSmol Interactive imageSMILES 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 OInChI 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 s1Key DVBUEXCIEIAXPM PJUQSVSOSA NSimilar 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 schizophrenia like psychotomimetic effects of NMDA receptor antagonists such as ketamine 5 See also EditList of investigational antidepressants Rapastinel ZelquistinelReferences Edit Naurex s Novel Antidepressant GLYX 13 Recognized as One of Windhover s Top 10 Neuroscience Projects to Watch PR Newswire 31 August 2010 a b Henter ID Park LT Zarate CA May 2021 Novel Glutamatergic Modulators for the Treatment of Mood Disorders Current Status CNS Drugs 35 5 527 543 doi 10 1007 s40263 021 00816 x PMC 8201267 PMID 33904154 Donello JE Banerjee P Li YX Guo YX Yoshitake T Zhang XL et al March 2019 Positive N Methyl D Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant Like Effects The International Journal of Neuropsychopharmacology 22 3 247 259 doi 10 1093 ijnp pyy101 PMC 6403082 PMID 30544218 Hayley S Litteljohn D November 2013 Neuroplasticity and the next wave of antidepressant strategies Frontiers in Cellular Neuroscience 7 218 doi 10 3389 fncel 2013 00218 PMC 3834236 PMID 24312008 a b c d e Naurex Reports Positive Top Line Phase 2b Results for Novel Antidepressant GLYX 13 and Advances NRX 1074 into Phase 2 Depression Study PR Newswire 6 May 2014 Archived from the original on 14 July 2014 Allergan Successfully Completes Naurex Acquisition Allergan plc Press release PR Newswire Retrieved 2016 11 20 Home Gate Neurosciences Retrieved 2022 05 12 Clinical trial number NCT02067793 for Study of Intravenous NRX 1074 in Patients With Major Depressive Disorder at ClinicalTrials gov Donello JE Banerjee P Li YX Guo YX Yoshitake T Zhang XL et al March 2019 Positive N Methyl D Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant Like Effects The International Journal of Neuropsychopharmacology 22 3 247 259 doi 10 1093 ijnp pyy101 PMC 6403082 PMID 30544218 External links EditApimostinel NRX 1074 AdisInsight Retrieved from https en wikipedia org w index php title Apimostinel amp oldid 1170112780, wikipedia, wiki, book, books, library,

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