GNE-495

MAP4K4 (IC50 = 3.7 nM)

GNE-495 是一种强效 MAP4K4 抑制剂，可以很好地促进血管生成。 GNE-495 表现出最低的身体稳定性、渗透性、有效的理想细胞平衡和 MAP4K4 吸附 [1]。

高剂量的 GNE-495（25 和 50 mg/kg）被腹腔注射给新生小鼠幼崽。在检查的每个物种中，GNE-495 都表现出良好的内部特性，包括低清除率、适度的终端半相衰减和适当的杠杆水平 (F=37–47%) [1]。

Rats, Mice and Pups
For the brain cassette study, three male Sprague-Dawley (SD) rats receive an intravenous (IV) bolus dose of six test substances (for example, GNE-495; 0.5 mg/kg). GNE-495 is injected intravenously in bolus doses of 1 mg/kg in female CD-1 mice for the mouse PK study. GNE-495 (5 mg/kg) is additionally injected intravenously (PO) into female CD-1 mice. The rat brain cassette PK is dosed at 2 mL/kg, and all other doses are administered at 5 mL/kg. Water and food are available to animals at all times, and they are not fasted before receiving a dose. Three blood samples (~60 μL) are taken from each mouse up to either 9 or 24 hours after the compound of interest is given. This is done using a serial sampling method, and it involves taking three blood samples from each mouse. After being mixed with K2EDTA and placed on ice or in a cold Kryorack immediately after collection, the blood is then centrifuged to separate the plasma. Blood samples are centrifuged for 10–15 minutes at 4°C while being spun at a speed of 1000-2000× g within an hour of being drawn. This process yields the plasma. The plasma samples are stored at -70 to -80°C until analysis. For neonate PK, 3-day-old CD1 pups are injected with 25 mg/kg and 50 mg/kg GNE-495. Blood samples are taken intraperitoneally at the times specified, retinas are taken one hour after the dose, snap frozen in liquid nitrogen, and kept at -80°C until analysis. The concentrations of plasma and retinal lysate are assessed using LC/MS/MS.

[1]. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015 Jun 29;6(8):913-8.

C22H20FN5O2

405.4249

405.16

C, 65.18; H, 4.97; F, 4.69; N, 17.27; O, 7.89

1449277-10-4

1449277-10-4

89730041

Yellow solid powder

1.5±0.1 g/cm3

734.5±60.0 °C at 760 mmHg

398.0±32.9 °C

0.0±2.4 mmHg at 25°C

1.712

2.54

101

2

6

4

30

668

0

FC1=C([H])C([H])=C([H])C(=C1[H])C1C([H])=C([H])C2=C(C(N([H])[H])=NC([H])=C2C(N([H])C2([H])C([H])([H])N(C2([H])[H])C(C2([H])C([H])([H])C2([H])[H])=O)=O)N=1

FYXCIBJXJYBWPX-UHFFFAOYSA-N

InChI=1S/C22H20FN5O2/c23-14-3-1-2-13(8-14)18-7-6-16-17(9-25-20(24)19(16)27-18)21(29)26-15-10-28(11-15)22(30)12-4-5-12/h1-3,6-9,12,15H,4-5,10-11H2,(H2,24,25)(H,26,29)

8-amino-N-[1-(cyclopropanecarbonyl)azetidin-3-yl]-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxamide

GNE 495; GNE495; GNE-495

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO: ~2.2 mg/mL (~5.4 mM)

配方 1 中的溶解度: ≥ 0.22 mg/mL (0.54 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 2.2 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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: ≥ 0.22 mg/mL (0.54 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 2.2mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，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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配方 3 中的溶解度: ≥ 0.22 mg/mL (0.54 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (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 2.2 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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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。