ACT001

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

ACT001  纯度: 98.85%

ACT001 是一种口服有效的 PAI-1 抑制剂，主要是通过抑制 PI3K 和 AKT 的磷酸化。ACT001 通过直接与 STAT3 结合来抑制 STAT3 的磷酸化和 PD-L1 表达。ACT001 是一种 DMAMCL (Micheliolide 的前药) 的富马酸盐形式，可以透过血脑屏障。ACT001 通过抑制胶质瘤中的 PI3K/AKT 通路与顺铂联合发挥协同作用。ACT001 具有有效的抗胶质母细胞瘤 (GBM) 活性和免疫调节作用。

ACT001

ACT001 Chemical Structure

CAS No. : 1582289-91-5

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥5280 In-stock
5 mg ￥4800 In-stock
10 mg ￥7500 In-stock
25 mg ￥15000 In-stock
50 mg   询价  
100 mg   询价  

* Please select Quantity before adding items.

ACT001 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Immunology/Inflammation Compound Library
  • JAK/STAT Compound Library
  • Kinase Inhibitor Library
  • Metabolism/Protease Compound Library
  • PI3K/Akt/mTOR Compound Library
  • Stem Cell Signaling Compound Library
  • Anti-Cancer Compound Library
  • CNS-Penetrant Compound Library
  • Autophagy Compound Library
  • Small Molecule Immuno-Oncology Compound Library
  • Anti-Aging Compound Library
  • Differentiation Inducing Compound Library
  • Oxygen Sensing Compound Library
  • Glycolysis Compound Library
  • Cytoskeleton Compound Library
  • Orally Active Compound Library
  • Glutamine Metabolism Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Lung Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Cancer Metabolism Compound Library
  • Anti-Obesity Compound Library
  • Angiogenesis Related Compound Library
  • Transcription Factor Targeted Library
  • Glucose Metabolism Compound Library
  • Anti-Liver Cancer Compound Library
  • Anti-Colorectal Cancer Compound Library

生物活性

ACT001 is an orally active PAI-1 inhibitor by inhibiting the phosphorylation of PI3K and AKT. ACT001 inhibits the phosphorylation of STAT3 and PD-L1 expression by directly binding to STAT3. ACT001, a fumarate salt form of DMAMCL (a prodrug of Micheliolide), can cross the blood-brain barrier. ACT001 exerts synergistic effects in combination with Cisplatin by inhibiting PI3K/AKT pathway in glioma. ACT001 has potent anti-glioblastoma (GBM) activity and immunomodulatory effects[1][2].

IC50 & Target[1][2]

p-STAT3

 

PI3K

 

Akt

 

体外研究
(In Vitro)

ACT001 (0-1000 μM; 24-96 hours) decreases cell viability when the concentration was higher than 10 μM in SNB19, U251MG cell lines[1].
ACT001 (10 μM; 48 h) can induce apoptosis in U118MG cells. ACT001 (3.75, 7.5 μM; 48 h) combined with Cisplatin (1-100 μM) increases the apoptosis of U118MG cells over either drug alone[2].
ACT001 (20-80 μM) decreases the expression of PD-L1 and phosphorylation of STAT3 in a dose-dependent manner[1].
ACT001 (10-40 μM) significantly decreases PD-L1 expression in a dose-dependent manner[1].
ACT001 (10 μM) inhibits the migration, invasion and vascular formation ability of U118MG cells[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: SNB19, U251MG and TJ179 cell lines
Concentration: 10, 100, 1000 μM
Incubation Time: 24, 48, 72, 96 hours
Result: Cell viability decreased when the concentration was higher than 10 μM, and the TJ179 cell line was most sensitive to high concentrations (40-80 μM).

Apoptosis Analysis[2]

Cell Line: U118MG cells
Concentration: 10 μM
Incubation Time: 48 hours
Result: Inducd apoptosis and that the inhibition effects cannot be enhanced by PAI-1 knockdown.

Western Blot Analysis[1]

Cell Line: SNB19, U251MG and TJ179 cell lines
Concentration: 20, 40, 80 μM
Incubation Time:
Result: Decreased the p-STAT3 level whereas the STAT3 level did not vary significantly from that of β-Actin.
Decreased PD-L1 expression relative to the expression of the loading control β-Actin.

RT-PCR[1]

Cell Line: SNB19, U251MG and TJ179 cell lines
Concentration: 10, 20, 40 μM
Incubation Time:
Result: Significantly decreased PD-L1 expression in a dose-dependent manner.

体内研究
(In Vivo)

ACT001 (100 or 400 mg/kg/day; Orally; starting on day 7 for 42 days) significantly causes survived longer than control mice and decreases p-STAT3 and PD-L1 expression with 400 mg/kg[1].
ACT001 (200 mg/kg/day; oral administration) enhances the antitumour effect of Cisplatin (2.5 mg/kg, once every 3 days, IP) in U118 xenograft model[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 immuno-competent mice (6 weeks old)[1]
Dosage: 100 or 400 mg/kg
Administration: Orally; every day starting on day 7 for 42 days
Result: Significantly caused survived longer than control mice with 400 mg/kg, and has no significant survival benefit with 100 mg/kg.
Decreases p-STAT3 and PD-L1 expression and inhibits the progression of glioma with 400 mg/kg.
Decreased M2 macrophage numbers and increases antitumor immune response with 400 mg/kg.

分子量

409.47

Formula

C21H31NO7
CAS 号

1582289-91-5
运输条件

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

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
溶解性数据
In Vitro: 

DMSO : 100 mg/mL (244.22 mM; ultrasonic and warming and heat to 60°C)

H2O : 100 mg/mL (244.22 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.4422 mL 12.2109 mL 24.4218 mL
5 mM 0.4884 mL 2.4422 mL 4.8844 mL
10 mM 0.2442 mL 1.2211 mL 2.4422 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2 mg/mL (4.88 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.88 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2 mg/mL (4.88 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.88 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2 mg/mL (4.88 mM); Clear solution

    此方案可获得 ≥ 2 mg/mL (4.88 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Luqing Tong, et al. ACT001 reduces the expression of PD-L1 by inhibiting the phosphorylation of STAT3 in glioblastoma. Theranostics. 2020 May 1;10(13):5943-5956.

    [2]. Xiaonan Xi, et al. ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma. Cell Death Dis. 2019 Oct 7;10(10):757.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务