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BYL-719

现货
Catalog No.
A8346
选择性的PI3Kα抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 900.00
现货
20mg
¥ 2,000.00
现货
100mg
¥ 7,040.00
现货

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Background

BYL719 is a selective PI3Kα inhibitor with IC50 of 5 nM. It has minimal effect on PI3Kβ, γ and δ[1]. Dysregulation of the PI3K signaling pathway is involved in multiple cancers. Among genes encoding different PI3K catalytic subunits, PIK3CA is mutated in many cancers. Therefore, PI3Kα-specific inhibitor may have anti-tumor activity in PI3Kα mutant cancers with fewer side effects compared to other pan-PI3K inhibitors.

BYL719 exhibited favorable pharmacokinetics and excellent oral bioavailability in animal models. In xenografts using nude mice, it showed dose-dependent effect of tumor inhibition[1]. It reduced proliferation and induced apoptosis in multiple myeloma cells which have higher expression of PIK3CA. The same study also observed synergistic effect between BYL719 and bortezomib or carfilzomib[2].

Clinical data suggests a disable safety profile with manageable side effects for BYL719. It also showed preliminary anti-tumor activity as a single agent in cancer patients[3]. This compound is currently tested in several clinical studies both as single agent and in combination with other agents.

References:
1. Furet P, Guagnano V, Fairhurst RA et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett 2013; 23: 3741-3748.
2. Azab F, Vali S, Abraham J et al. PI3KCA plays a major role in multiple myeloma and its inhibition with BYL719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance. Br J Haematol 2014; 165: 89-101.
3. Juric D, Argiles G, Burris H et al. Phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER+) metastatic breast cancer (MBC). Cancer Res 2012; 72: P6-10.

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
2. Han MW, Ryu IS, et al."Phosphorylation of PI3K regulatory subunit p85 contributes to resistance against PI3K inhibitors in radioresistant head and neck cancer." Oral Oncol. 2018 Mar;78:56-63. PMID:29496059

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt441.47
Cas No.1217486-61-7
FormulaC19H22F3N5O2S
SynonymsBYL 719; BYL719
Solubility≥22.1mg/mL in DMSO
Chemical Name(2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
SDFDownload SDF
Canonical SMILESCC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

多发性骨髓瘤细胞(OPM1、OPM2、RPMI8226、U266、MM1s、MM1R)和NCI-H9290

制备方法

溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

37℃

实验结果

BYL719显著降低PI3K信号蛋白pAKT、pS6R和pGSK的活化,在切片中也观察到这种作用,BYL719以剂量依赖性方式降低PI3K信号转导蛋白的表达。此外,BYL719以剂量依赖性方式引发MM细胞中的G1阻滞和诱导凋亡。

动物实验: [2]

动物模型

移植人成骨细胞骨肉瘤的5周龄雄性C57Bl/6J小鼠

给药剂量

口服,每日12.5–50 mg/kg

实验结果

BYL719以剂量依赖性方式显著减少肿瘤体积并减少异位骨肿瘤。此外,BYL719减少TRAP+破骨细胞的表面,而不影响osterix+细胞的数量。此外,BYL719减少KI67+细胞数量并减少肿瘤血管化。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Azab F, Vali S, Abraham J, Potter N et al. PI3KCA plays a major role in multiple myeloma and its inhibition with BYL719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance. Br J Haematol. 2014 Apr;165(1):89-101.

2. Gobin B, Huin MB, Lamoureux F et al. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96.

生物活性

描述 BYL719是一种有效的和选择性的PI3Kα抑制剂,IC50值为5 nM。
靶点 PI3Kα          
IC50 5 nM          

质量控制

化学结构

BYL-719

相关生物数据

BYL-719

相关生物数据

BYL-719

相关生物数据

BYL-719