Apimostinel (NRX1074; AGN241660)   中文名称: 阿普米司特

NMDA receptor

与 GLYX-13 类似，apimostinel (NRX-1074) 调节 NMDA 受体；然而，由于它是其中一种氨基酸的合成修饰，因此具有更高的功效和口服生物利用度[1]。

在临床前模型中，这两种药物似乎对一系列中枢神经系统疾病特别有效[1]。

Apimostinel (NRX-1074/AGN-241751) is a higher-potency rapastinel analog with increased bioavailability.
NRX-1074 modulates the NMDA receptor in a similar fashion to GLYX-13, but has a synthetic modification to one of the amino acids, conferring increased potency and oral bioavailability

[1]. Naurex's First Orally Active Molecule, NRX-1074, Demonstrates Statistically Significant Improvement in Depression Scores within 24 Hours in Phase 2 Study for Major Depressive Disorder. January 28, 2015.

NRX-1074 has been used in trials studying the treatment of Schizophrenia.

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Naurex reported today that the first efficacy trial for NRX-1074, using a single-dose IV administration of a compound that will be delivered orally from now on, established a remarkable degree of immediate impact. At 24 hours post-injection of the highest dose (and unlike GlyX-13, NRX-1074 does not have an inverted-U doseresponse curve), the mean reductionin Hamilton scores was 14 points, the effect size was .88. The effect size itself, just 24 hours later, is impressive compared to current antidepressants. It was also pleasantly surprising that 72% of patients receiving NRX-1074 showed a ‘clinically meaningful’ response, given that in rapastinel/GlyX13’s PhIIb, only about half of the patients appeared to be treatment responsive. The usual caveats--small treatment samples for each of the three doses, 35 patients; just a single-dose readout; IV delivery of this oral compound--do apply, and the data release did not offer anything regarding the durability of the antidepressant response. However, durability is far less important here than it was with IV GlyX-13, for which minimizing the frequency of re-infusion would be an important treatment consideration. These data at 24 hours suggest that once-daily administration would be viable, the sweet spot for an oral antidepressant. The next clinical step (starting this spring) will be a repeated-dose, oral administration trial of NRX-1074, as monotherapy-- in contrast to GlyX-13, being developed as an adjunct. As to the next corporate development step, it seems a near-certainty that Naurex will go the IPO route to funding their ambitious clinical development agenda--the question to us is not whether, but when.[1]

C25H37N5O6

503.59

503.274

C, 59.63; H, 7.41; N, 13.91; O, 19.06

1421866-48-9

1421866-48-9;

71249967

White to off-white solid powder

1.3±0.1 g/cm3

878.7±65.0 °C at 760 mmHg

485.2±34.3 °C

0.0±0.3 mmHg at 25°C

1.608

0.22

179

5

7

9

36

834

6

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

DVBUEXCIEIAXPM-PJUQSVSOSA-N

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

(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

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.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~155 mg/mL (~307.79 mM)
H2O : ≥ 6.67 mg/mL (~13.24 mM)

配方 1 中的溶解度: ≥ 7.75 mg/mL (15.39 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 77.5 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 7.75 mg/mL (15.39 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 77.5 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。