| Size | Price | Stock | Qty |
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Purity: ≥98%
Apimostinel (NRX-1074; AGN-241660) is a novel and orally bioactive antidepressant which acts as a selective partial agonist of an allosteric site of the glycine site of the NMDA receptor complex, which is under investigation by Naurex (recently acquired by Allergan) for the treatment of major depressive disorder. Its mechanism of action and effects are similar to those of rapastinel (GLYX-13), which is under development as an adjunctive therapy for treatment-resistant depression also by Naurex; however, NRX-1074 is 100-fold more potent by weight and, unlike GLYX-13 (which must be administered via intravenous injection), is orally -active.
| Targets |
NMDA receptor
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|---|---|
| ln Vitro |
Similar to GLYX-13, apimostinel (NRX-1074) regulates NMDA receptors; however, because it is a synthetic modification of one of the amino acids, it has a higher efficacy and oral bioavailability [1].
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| ln Vivo |
In preclinical models, both drugs appear to be particularly effective against a range of central nervous system illnesses [1].
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| ADME/Pharmacokinetics |
Aspirinusine (NRX-1074/AGN-241751) is a more potent lapasteurine analogue with higher bioavailability. NRX-1074 modulates the NMDA receptor in a manner similar to GLYX-13, but one of its amino acids is synthetically modified, thereby improving potency and oral bioavailability.
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| References | |
| Additional Infomation |
NRX-1074 is being investigated in clinical trials for the treatment of schizophrenia. Naurex reported today that the first efficacy trial of NRX-1074 (using a single intravenous injection, the compound will later be administered orally) showed significant immediate efficacy. Twenty-four hours after the highest dose (unlike GlyX-13, NRX-1074's dose-response curve is not an inverted U-shape), the Hamilton Depression Rating Scale score decreased by an average of 14 points, with an effect size of 0.88. Such a significant effect size after only 24 hours is impressive compared to current antidepressants. Furthermore, encouragingly, 72% of patients treated with NRX-1074 showed a "clinically meaningful" response, compared to only about half of the patients in the Phase IIb clinical trial of rapastinel/GlyX-13. Common limitations remain—the sample size for each of the three dose groups was small, totaling 35 patients; only a single dose was administered; the oral compound was administered intravenously—and this data release did not provide information on the durability of the antidepressant effect. However, durability of effect is less important here compared to intravenous GlyX-13, as minimizing the frequency of repeated infusions is an important therapeutic consideration for GlyX-13. These 24-hour data suggest that a once-daily dosing regimen is feasible, which is optimal for oral antidepressants. The next clinical trial (to begin this spring) will be a repeated-dose oral trial of NRX-1074 monotherapy—in contrast to GlyX-13, which is being developed as an adjunctive therapy. As for the company’s next steps, Naurex will almost certainly opt for an IPO to raise funds for its ambitious clinical development plans—for us, the question is not whether it will go public, but when. [1]
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| Molecular Formula |
C25H37N5O6
|
|---|---|
| Molecular Weight |
503.59
|
| Exact Mass |
503.274
|
| Elemental Analysis |
C, 59.63; H, 7.41; N, 13.91; O, 19.06
|
| CAS # |
1421866-48-9
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| Related CAS # |
1421866-48-9;
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| PubChem CID |
71249967
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
878.7±65.0 °C at 760 mmHg
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| Flash Point |
485.2±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.608
|
| LogP |
0.22
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| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
36
|
| Complexity |
834
|
| Defined Atom Stereocenter Count |
6
|
| SMILES |
O=C([C@@H]1CCCN1C([C@H]([C@@H](C)O)N)=O)N1CCC[C@]1(C(N[C@H](C(N)=O)[C@@H](C)O)=O)CC1C=CC=CC=1
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| InChi Key |
DVBUEXCIEIAXPM-PJUQSVSOSA-N
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| InChi Code |
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
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| Chemical 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
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| Synonyms |
NRX-1074; NRX 1074; Apimostinel; NRX-1074; Apimostinel [USAN]; UNII-TTT1F11FZB; Apimostinel (USAN); NRX1,074; APIMOSTINEL [INN]; ...; 1421866-48-9; NRX1074; AGN-241660; AGN241660; AGN 241660.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~155 mg/mL (~307.79 mM)
H2O : ≥ 6.67 mg/mL (~13.24 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.75 mg/mL (15.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 77.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 7.75 mg/mL (15.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 77.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9857 mL | 9.9287 mL | 19.8574 mL | |
| 5 mM | 0.3971 mL | 1.9857 mL | 3.9715 mL | |
| 10 mM | 0.1986 mL | 0.9929 mL | 1.9857 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06400121 | NOT YET RECRUITING | Drug: Apimostinel Infusion, Intravenous Behavioral: Cognitive Training Behavioral: Sham Training Drug: Lactated Ringers, Intravenous |
Depression | Rebecca Price | 2024-09-01 | Phase 2 |
| NCT05597241 | COMPLETED | Drug: apimostinel Drug: Placebo |
Major Depressive Disorder | Gate Neurosciences, Inc | 2022-10-15 | Phase 1 |
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