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CAS No.: 1430844-80-6

A-1331852 Catalog No. CSN18735

A1331852 is a potent and selective BCL-XL inhibitor and may be useful in the treatment of cancer, immune and autoimmune diseases.

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 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].

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.

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实验方案

计算器摩尔计算器总药量计算器工作液计算器

储存液制备

1 mg

5 mg

10 mg

1 mM

1.5179 mL

7.5894 mL

15.1789 mL

5 mM

0.3036 mL

1.5179 mL

3.0358 mL

10 mM

0.1518 mL

0.7589 mL

1.5179 mL

技术信息

CAS号 1430844-80-6 储存条件

粉末

Sealed in dry,Room Temperature

液体

-20°C:3-6 月 -80°C:12月

分子式 C38H38N6O3S 运输蓝冰

分子量 658.81 别名

溶解度
DMSO 100.0 mg/mL (151.8 mM)
Water Insoluble
Ethanol Insoluble
动物实验配方

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靶点 Description IC50
Bcl-xL Ki:0.01 nM

A-1331852 Catalog No. CSN18735

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