2. PI3K/Akt/mTOR Stem Cell/Wnt Neuronal Signaling
  3. GSK-3 Tau Protein Amyloid-β β-catenin
  4. Multitarget AD-IN-7

Multitarget AD-IN-7 是一种具有口服活性的多重靶点的抗 AD 化合物。 Multitarget AD-IN-7 表现出 GSK-3β、GSK-3α 抑制活性 (IC50 = 0.66、0.83 nM)。Multitarget AD-IN-7 可上调 p-GSK-3β-Ser9 的表达，抑制 tau-Ser396 磷酸化，靶向作用于 Aβ1-42，螯合致病性金属离子，清除 ABTS•+，上调 β-catenin 及神经发生生物标志物的表达，促进神经突生长。Multitarget AD-IN-7 提升阿尔茨海默病斑马鱼的运动能力。Multitarget AD-IN-7 可用于阿尔茨海默病的相关研究。

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Multitarget AD-IN-7

Multitarget AD-IN-7 Chemical Structure

CAS No. : 3113741-59-3

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GSK-3 GSK-3α GSK-3β

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

Multitarget AD-IN-7 is an orally active multi-target anti-AD compound. Multitarget AD-IN-7 exhibits inhibitory activity against GSK-3β and GSK-3α (IC50 = 0.66, 0.83 nM). Multitarget AD-IN-7 upregulates the expression of p-GSK-3β-Ser9, inhibits the phosphorylation of tau-Ser396, targets Aβ1-42, chelates pathogenic metal ions, scavenges ABTS•+, upregulates the expression of β-catenin and neurogenesis biomarkers, and promotes neurite outgrowth. Multitarget AD-IN-7 improves motor ability in Alzheimer's disease zebrafish. Multitarget AD-IN-7 is applicable to research related to Alzheimer's disease[1].

IC50 & Target[1]

GSK-3β

0.66 nM (IC50)

GSK-3α

0.83 nM (IC50)

体外研究
(In Vitro)

Multitarget AD-IN-7 (Compound 3c) 在包含 24 种激酶的筛选组中对 GSK-3β/α 表现出良好的选择性，其对 GSK-3α 的 IC50 为 0.83 nM，对 CDK5/p35 的 IC50 为 928 nM[1]。
Multitarget AD-IN-7 (1-10 μM; 2.5 h) 上调 p-GSK-3β-Ser9 水平，从而使 SH-SY5Y 细胞中的 GSK-3β 失活，上调 SH-SY5Y 细胞中的 β-catenin 水平[1]。
Multitarget AD-IN-7 (1-10 μM; 1 h pre-incubation before 6 h Aβ25-35 stimulation) 可在体外以浓度依赖的方式抑制 SH-SY5Y 细胞中 Aβ25-35 (HY-P0128) 诱导的 tau-Ser396 磷酸化[1]。
Multitarget AD-IN-7 (10 μM; 24 h) 可上调 SH-SY5Y 细胞中神经发生相关生物标志物 GAP-43 和 MAP-2 的 mRNA 表达水平[1]。
Multitarget AD-IN-7 (1 μM; 72 h) 可促进 SH-SY5Y 细胞的轴突生长，使带有轴突的细胞比例提升至 44.11%[1]。
Multitarget AD-IN-7 (20 μM mixed with 40 μM metal ions; 30 min ambient temperature) 可与阿尔茨海默病 (AD) 相关金属离子 Fe2+、Zn2+、Cu2+ 及 Al3+ 发生强螯合作用 (但不与 Na+、K+、Mg2+、Ca2+ 螯合)[1]。
Multitarget AD-IN-7 (20 μM mixed with 20 μM Aβ1-42; 24 h 37 °C) 经 ThT 荧光实验和透射电子显微镜 (TEM) 检测，可抑制 Aβ1-42 的自聚集，抑制率达 33.35%，使预形成的 Aβ1-42 聚集体解聚 46.48%[1]。
Multitarget AD-IN-7 (20 μM mixed with 20 μM Aβ1-42 and 20 μM Cu2+; 24 h 37 °C) 经 ThT 荧光检测显示，可抑制 Cu2+ 介导的 Aβ1-42 聚集达 52.18%，使预先形成的 Cu2+-Aβ1-42 聚集体的解聚率达到 56.12%[1]。
Multitarget AD-IN-7 清除 ABTS•+ 的 IC50 为 7.04 μM[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Multitarget AD-IN-7 相关抗体:

Western Blot Analysis[1]

Cell Line: SH-SY5Y cells
Concentration: 1, 5, 10 μM
Incubation Time: 2.5 h
Result: Increased p-GSK-3β-Ser9 levels in a concentration-dependent manner, with p-GSK-3β-Ser9/GAPDH ratios of 0.43, 0.63, and 0.76 for 1, 5, 10 μM, respectively.\nIncreased β-catenin levels in a concentration-dependent manner, with β-catenin/GAPDH ratios of 0.32, 0.39, and 0.51 for 1, 5, 10 μM, respectively.

Western Blot Analysis[1]

Cell Line: SH-SY5Y cells
Concentration: 1, 5, 10 μM
Incubation Time: 1 h (pre-incubation before 6 h Aβ25-35 stimulation)
Result: Decreased p-tau-Ser396 levels in a concentration-dependent manner, with p-tau-Ser396/GAPDH ratios of 0.31, 0.24, and 0.18 for 1, 5, 10 μM, respectively.

RT-PCR[1]

Cell Line: SH-SY5Y cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Upregulated mRNA expression of GAP-43 and MAP-2 to levels greater than the positive control retinoic acid.
体内研究
(In Vivo)

Multitarget AD-IN-7 (1.95-7.81 μM; water exposure; 24 h) 可呈剂量依赖性增强 AlCl3 诱导的阿尔茨海默病斑马鱼的运动能力[1]。
Multitarget AD-IN-7 (1000 mg/kg；口服；单次) 在 C57BL/6 小鼠中表现出低急性毒性，单次口服剂量为 1000 mg/kg 时，14 天内未观察到死亡、行为异常、体重变化或器官病理改变[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: AB wild-type (juvenile, 4 days post-fertilization)[1]
Dosage: 1.95 μM; 3.91 μM; 7.81 μM
Administration: water exposure; 24 h
Result: Increased swimming distance of AlCl3-induced AD zebrafish to 1314 mm at 1.95 μM.
Increased swimming distance of AlCl3-induced AD zebrafish to 1716 mm at 3.91 μM.
Increased swimming distance of AlCl3-induced AD zebrafish to 2040 mm at 7.81 μM, compared to the AlCl3-induced control distance of 996 mm.
Animal Model: C57BL/6 (6-8 weeks old, male and female)[1]
Dosage: 1000 mg/kg
Administration: p.o.; single dose
Result: Observed no mortalities or abnormal behaviors over 14 days.
Showed no marked body weight changes compared to controls.
Observed no noticeable size or shape differences in dissected organs (heart, liver, spleen, lung, kidney, brain).
Revealed no significant pathological changes in organs via H&E staining.
分子量

457.48

Formula

C28H19N5O2
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

Multitarget AD-IN-7 相关分类

  • 摩尔计算器

  • 稀释计算器

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Multitarget AD-IN-73113741-59-3GSK-3Tau ProteinAmyloid-ββ-cateninGlycogen synthase kinase-3Glycogen synthase kinase 3β-amyloid peptideAβAbetaBeta cateninMulti-target AD inhibitorsAlzheimer's diseaseSH-SY5Y cellsZebrafishC57BL/6 miceInhibitorinhibitorinhibit

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