BYL-719
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
BYL719是一种有效的和选择性的PI3Kα抑制剂,IC50值为5 nM,对PI3Kβ、γ和δ的作用最小[1]。PI3K信号通路的失调参与多种癌症的发生。在编码不同PI3K催化亚基的基因中,PIK3CA突变发生在许多癌症中。因此,PI3Kα特异性的抑制剂在PI3Kα突变的癌症中具有抗癌活性,与其它广谱的PI3K抑制剂相比,副作用也较少。
BYL719具有良好的药代动力学特性和在动物模型中优异的口服生物利用度。在异种移植裸鼠中,BYL719剂量依赖性地抑制肿瘤的生长[1]。在过表达PIK3CA的多发性骨髓瘤细胞中,BYL719减少细胞增殖,诱导细胞凋亡。同样的研究发现,BYL719与bortezomib或 carfilzomib之间有协同效应[2]。
临床数据表明,BYL719具有禁用安全性,其副作用是可控的。在癌症病人中,BYL719单独给药也展示了初步的抗肿瘤活性[3]。BYL719目前正用于临床研究,作为单一药剂或与其它药剂联合使用。
参考文献:
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.
- 1. A Thole, B Thibault, et al. "The lipid kinase PI3Kα is required for aggregation and survival of intraperitoneal cancer cells." bioRxiv. 2019 September 23.
- 2. Chen H, Wong CC, et al. "APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target." Theranostics. 2019 Jul 9;9(18):5246-5260. PMID:31410213
- 3. 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
- 4. 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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 441.47 |
Cas No. | 1217486-61-7 |
Formula | C19H22F3N5O2S |
Synonyms | BYL 719; BYL719 |
Solubility | ≥22.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
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 |
SDF | Download SDF |
Canonical SMILES | CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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 |
质量控制和MSDS
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