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 (HY-17394) 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 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 (HY-17394) by inhibiting PI3K/AKT pathway in glioma. ACT001 has potent anti-glioblastoma (GBM) activity and immunomodulatory effects.

Solid-liquid mixture

p-STAT3 PI3K

ACT001 (0-1000 μM; 24-96 hours) decreases cell viability when the concentration is higher than 10 μM in SNB19, U251MG cell lines.
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.
ACT001 (20-80 μM) decreases the expression of PD-L1 and phosphorylation of STAT3 in a dose-dependent manner.
ACT001 (10-40 μM) significantly decreases PD-L1 expression in a dose-dependent manner.
ACT001 (10 μM) inhibits the migration, invasion and vascular formation ability of U118MG cells.
has not independently confirmed the accuracy of these methods. They are for reference only.

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

Room temperature in continental US; may vary elsewhere.

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)

[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.

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