产品说明书

A-1331852

Print
Chemical Structure| 1430844-80-6 同义名 : -
CAS号 : 1430844-80-6
货号 : A206174
分子式 : C38H38N6O3S
纯度 : 99%+
分子量 : 658.812
MDL号 : MFCD30532662
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(75.89 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 4 mg/mL(6.07 mM)，配合低频超声，并水浴加热至45℃助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：
生物活性
靶点

  • Bcl-xL

    Bcl-xL, Ki:<0.01 nM
描述 B-cell lymphoma-extra-large (Bcl-xL) is an anti-apoptotic Bcl-2 protein found in the mitochondrial membrane. Bcl-xL is reported to support normal brain development and protects neurons against toxic stimulation during pathological process via its roles in regulation of mitochondrial functions[1]. A1331852 is a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL-dependent tumor cells, and may be useful in the treatment of cancer, immune and autoimmune diseases[2]. In hepatoma, cell lines and Hep3B liver spheroids, regorafenib cytotoxicity was potentiated by BCL-xL siRNA transfection or pharmacological inhibition (A-1331852). Mitochondrial outer membrane permeabilization, cytochrome c release, and caspase-3 activation mediated A-1331852/regorafenib-induced cell death. In a patient-derived xenograft (PDX) HCC model, BCL-xL inhibition stimulated regorafenib activity, drastically decreasing tumor growth. Moreover, regorafenib-resistant HepG2 cells displayed increased BCL-xL and reduced MCL-1 expression, while A-1331852 reinstated regorafenib efficacy in vitro and in a xenograft mouse model[3]. A-1331852/S63845 co-treatment synergistically induces rapid intrinsic apoptosis in vitro and demonstrates efficiency in an in vivo embryonic chicken model of rhabdomyosarcoma[4].Treatment of multidrug resistance 2 gene knockout (Mdr2-/- ) mice with A-1331852 resulted in an 80% decrease in senescent cholangiocytes, a reduction of fibrosis-inducing growth factors and cytokines, decrease of α-smooth muscle actin-positive ASFs, and in a significant reduction of liver fibrosis[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.52mL

0.30mL

0.15mL

7.59mL

1.52mL

0.76mL

15.18mL

3.04mL

1.52mL
参考文献

[1]Han-A Park. et al. Nutritional Regulators of Bcl-xL in the Brain. Molecules. 2018. 23(11), 3019.

[2]Le Wang,et al. Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-X L Inhibitor. ACS Med Chem Lett. 2020. 11(10), 1829-1836.

[3]Blanca Cucarull,et al. Regorafenib Alteration of the BCL-xL/MCL-1 Ratio Provides a Therapeutic Opportunity for BH3-Mimetics in Hepatocellular Carcinoma Models. Cancers (Basel). 2020. 2(2), 332.

[4]Sarah Kehr,et al. Targeting BCL-2 proteins in pediatric cancer: Dual inhibition of BCL-X L and MCL-1 leads to rapid induction of intrinsic apoptosis. Cancer Lett. 2020. 482, 19-32.

[5]Anja Moncsek,et al. Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2 -/- ) mice. Hepatology. 2018. 67(1), 247-259.