规格 | 价格 | 库存 | 数量 |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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靶点 |
GSK-3β (IC50 = 6.7 nM); GSK-3α (IC50 = 10 nM); ATM (cdc2 = 8800 nM)
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体外研究 (In Vitro) |
Laduviglusib triHClide 抑制人 GSK-3β,Ki 值为 9.8 nM[1]。 Laduviglusib triHClide 是一种微小的有机分子,通过争夺 ATP 结合位点来抑制 GSK3α 和 GSK3β。根据体外激酶测定,Laduviglusib triHClide 特异性抑制 GSK3β (IC50=~5 nM) 和 GSK3α (IC50=~10 nM),对其他激酶影响很小[4]。 Laduviglusib triHClide 在 2.5 μM 时使 ES-D3 细胞的活力降低 24.7%,在 5 μM 时降低 56.3%,在 7.5 μM 时降低 61.9%,在 10 μM 时降低 69.2%,IC50 为 4.9 M[2]。
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体内研究 (In Vivo) |
单次口服剂量后,Laduviglusib(16 mg/kg 或 48 mg/kg)三盐酸盐可迅速降低 ZDF 大鼠的血浆葡萄糖,给药后 3-4 小时最大降幅接近 150 mg/dl[1]。放射前 4 小时给予一次 laduviglusib (2 mg/kg) 三盐酸盐,可显着提高 14.5 Gy 腹部放射 (ABI) 后的生存率。用 laduviglusib triHClide 治疗可显着减少隐窝凋亡,防止 p-H2AX+ 细胞的积聚,并增强隐窝再生和绒毛高度。用 laduviglusib triHClate 治疗可通过防止细胞凋亡来提高 Lgr5+ 细胞的存活率,并成功延迟早在 4 小时内 Olfm4、Lgr5 和 CD44 的丢失[5]。
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细胞实验 |
细胞活力的丧失与 MTT 活性的下降相关,MTT 活性是一种可靠的基于代谢的估计细胞活力的测试。在含有 LIF 的 ES 细胞培养基中,将 2,000 个细胞接种在涂有明胶的 96 孔板上过夜。第二天将培养基更换为不含 LIF 且血清含量减少的培养基。它还补充有 0.1-1 μM BIO、或 1-10 μM SB-216763、CHIR-99021 或 CHIR-98014。作为对照,使用不含 DMSO 或 GSK3 抑制剂的基础培养基。分析了每个测试条件的三个副本[3]。
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动物实验 |
Rats[1]:
Primary hepatocytes from male Sprague Dawley rats that weighed <140 g are prepared and used 1-3 h after isolation. Centrifuged and lysed by freeze/thaw in buffer A plus 0.01% NP40, aliquots of 1106 cells in 1 mL of DMEM/F12 medium plus 0.2% BSA and CHIR-99021 (orally at 16 or 48 mg/kg) or controls are incubated in 12-well plates for 30 min at 37°C in a CO2-enriched atmosphere. The GS assay is then carried out once more.
Mice[4]:
The mice used are 6–10 week old mice. The PUMA+/+ and PUMA-/- littermates of Lgr5-EGFP (Lgr5-EGFP-IRES-creERT2) mice are either given abdominal irradiation (ABI) or whole body irradiation (TBI) to induce radiation sickness. Two milligrams per kilogram of CHIR99021 or one milligram per kilogram of SB415286 are intraperitoneally (i.p.) injected into mice four hours prior to radiation treatment. Small intestines are removed from sacrificed mice and subjected to western blotting and histology tests. Before being sacrificed, all mice receive an intraperitoneal injection of 100 mg/kg BrdU.
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参考文献 |
分子式 |
C22H21CL5N8
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分子量 |
574.72
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精确质量 |
574.72
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元素分析 |
C, 45.98; H, 3.68; Cl, 30.84; N, 19.50
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CAS号 |
1782235-14-6
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相关CAS号 |
Laduviglusib;252917-06-9;Laduviglusib monohydrochloride;1797989-42-4
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外观&性状 |
Solid powder
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SMILES |
CC1=CN=C(N1)C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)Cl)NCCNC4=NC=C(C=C4)C#N.Cl.Cl.Cl
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InChi Key |
DSFVSCNMMZRCIA-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C22H18Cl2N8.3ClH/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19;;;/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32);3*1H
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化学名 |
6-[2-[[4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino]ethylamino]pyridine-3-carbonitrile;trihydrochloride
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别名 |
CHIR-73911 3HCl; CHIR911;CHIR 911; CT- 99021; CT-99021; CHIR73911; CHIR 73911 trihydrochloride; CHIR-911; CT- 99021; GSK 3 inhibitor XVI; GSK 3IXV; CHIR99021; CHIR 99021
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
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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溶解度 (体外) |
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溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.62 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 20.8 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: ≥ 2.08 mg/mL (3.62 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7400 mL | 8.6999 mL | 17.3998 mL | |
5 mM | 0.3480 mL | 1.7400 mL | 3.4800 mL | |
10 mM | 0.1740 mL | 0.8700 mL | 1.7400 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。