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Alpelisib

Alpelisib

产品编号 T1921   CAS 1217486-61-7
别名: BYL-719

Alpelisib 是一种选择性的,有效的,具有口服活性的PI3Kα抑制剂,具有抗肿瘤活性。它对 PIK3CA 突变癌具有靶向性。它抑制 p110α (IC50:5 nM)、p110γ (IC50:250 nM)、p110δ (IC50:290 nM)、p110β (IC50:1200 nM)。

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Alpelisib, CAS 1217486-61-7
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产品目录号及名称: Alpelisib (T1921)
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选择批次  
纯度: 99.62%
纯度: 99.25%
纯度: 99.07%
纯度: 98%
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生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Alpelisib is an orally bioavailable PI3Kα inhibitor (IC50: 5 nM in a cell-free assay) with potential antineoplastic activity and minimal effect on PI3Kβ/γ/δ.
靶点活性 p110α:5 nM (cell free), p110γ:250 nM (cell free)
体外活性 In biochemical assays, Alpelisib (NVP-BYL719) inhibits wild-type PI3Kα (IC50: 4.6 nmol/L) more potently than the PI3Kδ (IC50: 290 nmol/L) and PI3Kγ (IC50: 250 nmol/L) isoforms and shows significantly reduced activity against PI3Kβ (IC50: 1,156 nmol/L). Here, in addition, we show that NVP-BYL719 potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC50~4 nmol/L). NVP-BYL719 potently inhibited Akt phosphorylation in cells transformed with PI3Kα (IC50: 74 ± 15 nmol/L) and showed significantly reduced inhibitory activity in PI3Kβ or PI3Kδ isoforms transformed cells (≥15-fold compared with PI3Kα) [1]. After 72 hr of treatment, BYL719 significantly inhibited the cell growth of all osteosarcoma cell lines tested in a dose-dependent manner with an IC50 ranging from 6 to 15 mM and with the IC90 from 24 to 42 mM at 72 hr [2].
CellLine: HSA cells
Concentration: 20μM
IncubationTime: 8h
Result: Only the Re21 cells recovered almost completely from the wound after 8 h; the JuA1 and JuB4 cells exhibited a significantly delayed wound healing ability.
CellLine: HK2 cells
Concentration: 10μM
IncubationTime: 16h
Result: Alpelisib reduced the actin baskets in OCRL KO HK2 cells in a dose-responsive fashion.
体内活性 NVP-BYL719 (12.5, 25, or 50 mg/kg, p.o.) treatment was associated with dose and time-dependent inhibition of the PI3K/Akt pathway, which notably paralleled time-dependent drug exposure in tumor and plasma. Rat1-myr-p110α tumor-bearing nude mice were treated orally every day with the compound for up to 8 consecutive days. Treatments of 12.5, 25, and 50 mg/kg were well tolerated and resulted in a dose-dependent and statistically significant antitumor effect [1]. BYL719 significantly reduced tumor volumes in a dose-dependent manner compared to a vehicle group (p < 0.01 and p < 0.001, respectively for 12.5 and 50 mg/kg BYL719) [2].
Animal Model: Eight-week-old male Sprague–Dawley rats weighing 250–300 g
Dosage: 1 and 10mg/kg
Administration: Intravenous; 8h
Result: The plasma levels of alpelisib declined in a multi-exponential manner, with a t1/2 of 147–297 min. The dose-normalized AUC of alpelisib was significantly different between the doses; the values were 87.3 ± 21.3 and 134 ± 25 μg·min/mL for 1 and 10 mg/kg
Animal Model: OcrlY/− mice
Dosage: 50mg/kg
Administration: Oral gavage for 6 weeks
Result: Reducted in growth rate relative.
细胞实验 To evaluate the isoform-specific potency of NVP-BYL719 in a cell-based system, an N-terminally myristoylated form of each PI3K class IA isoform was expressed in Rat1 fibroblasts. The retroviral expression plasmid pBabePuro containing human p110α, p110β, and p110δ with an N-terminal myristoylation (myr) signal followed by an HA-tag were generated. Successfully infected Rat1 cells were selected in medium containing 4 μg/mL of puromycin, expanded and characterized for expression of the p110 isoforms. Transgenic expression of the myristoylated protein was confirmed by increased levels of phosphorylated Akt [1].
动物实验 All in life experimentation and efficacy studies were conducted as described previously. Tumor xenografts were grown subcutaneously or orthotopically in nude mice or nude Rowett rats (Hsd: RH-Fox1rnu) by injection of 3 × 10^6 to 1 × 10^7 cells or implantation of tumor fragments of approximately 50 mg. Tumor-bearing animals mice were treated with either vehicle control, NVP-BYL719, or NVP-BKM120 (p.o., every day) at the doses indicated [1].
别名 BYL-719
分子量 441.47
分子式 C19H22F3N5O2S
CAS No. 1217486-61-7

存储

Powder: -20°C for 3 years | In solvent: -80°C for 2 years

溶解度

DMSO: 82 mg/mL (185.7 mM)

Ethanol: 2 mg/mL (4.53 mM)

( < 1 mg/mL refers to the product slightly soluble or insoluble )

参考文献

1. Fritsch C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29. 2. Gobin B, 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. 3. Young CD, et al. Conditional loss of ErbB3 delays mammary gland hyperplasia induced by mutant PIK3CA without affecting mammary tumor latency, gene expression, or signaling. Cancer Res. 2013 Jul 1;73(13):4075-85. 4. Elkabets M, et al. mTORC1 inhibition is required for sensitivity to PI3K p110α inhibitors in PIK3CA-mutant breast cancer. Sci Transl Med. 2013 Jul 31;5(196):196ra99. 5. Yang T, Xu R, Su Q, et al. Chelerythrine hydrochloride inhibits proliferation and induces mitochondrial apoptosis in cervical cancer cells via PI3K/BAD signaling pathway[J]. Toxicology in Vitro. 2020, 68: 104965. 6. Liao W, Wang Z, Han Y, et al. Design, synthesis and biological activity of novel 2, 3, 4, 5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity[J]. European Journal of Medicinal Chemistry. 2020: 112309.

文献引用

1. Liao W, Wang Z, Han Y, et al. Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity. European Journal of Medicinal Chemistry. 2020, 197: 112309 2. Yang T, Xu R, Su Q, et al. Chelerythrine hydrochloride inhibits proliferation and induces mitochondrial apoptosis in cervical cancer cells via PI3K/BAD signaling pathway. Toxicology in Vitro. 2020, 68: 104965. 3. Chen R, Wang Z, Sima L, et al.Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3K α inhibitors.Journal of Enzyme Inhibition and Medicinal Chemistry.2023, 38(1): 2155638.
Duvelisib (R enantiomer) hydrochloride PI3K/Akt/mTOR-IN-2 TGX-115 PI3Kα/mTOR-IN-1 Urea, N-[4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-N'-3-pyridinyl- Torbafylline PI5P4Ks-IN-2 GSK2292767 FA

相关化合物库

该产品包含在如下化合物库中:
抗氧化化合物库 氧化还原化合物库 抗衰老化合物库 已知活性化合物库 抗癌活性化合物库 干细胞分化化合物库 抑制剂库 糖酵解化合物库 代谢化合物库 FDA 上市药物库

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请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

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Keywords

Alpelisib 1217486-61-7 PI3K/Akt/mTOR signaling PI3K Inhibitor Phosphoinositide 3-kinase inhibit phosphorylation p110α cancer BYL 719 BYL-719 antineoplastic AKT metastasis mutant BYL719 PIK3CA breast inhibitor

 

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