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Pilaralisib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Pilaralisib图片
CAS NO:934526-89-3
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议

产品名称
XL-147
SAR245408
产品介绍
Pilaralisib (XL147; SAR245408) 是一种有效的选择性 I 类PI3Ks 抑制剂,抑制 PI3Kα,PI3Kβ,PI3Kγ 和 PI3Kδ,IC50分别为 39 nM,383 nM,23 nM 和 36 nM。
生物活性

Pilaralisib (XL147; SAR245408) is a potent and highly selective class IPI3Ks inhibitor withIC50s of 39 nM, 383 nM, 23 nM and 36 nM forPI3Kα,PI3Kβ,PI3Kγ, andPI3Kδ.

IC50& Target

PI3Kα

39 nM (IC50)

PI3Kβ

383 nM (IC50)

PI3Kδ

36 nM (IC50)

PI3Kγ

23 nM (IC50)

Vps34

6974 nM (IC50)

DNA-PK

4750 nM (IC50)

体外研究
(In Vitro)

Pilaralisib (XL147) displays potent inhibitory activity against Class I PI3K isoforms p110α, p110δ, and p110γ, with IC50s of 39, 36, and 23 nM, respectively. Pilaralisib (XL147) is less potent against the remaining Class I isoform, p110β, with an IC50value of 383 nM. The IC50value for inhibition of PI3Kα by Pilaralisib (XL147) is determined at various concentrations of ATP, revealing XL147 to be an ATP-competitive inhibitor with an equilibrium inhibition constant (Ki) value of 42 nM. Pilaralisib (XL147) has relatively weak inhibitory activity toward the class III PI3K vacuolar sorting protein 34 (VPS34; IC50value of ~7.0 M) and the PI3K-related DNA-dependent protein kinase (DNA-PK; IC50value of 4.75 μM). In an mTOR kinase immunoprecipitation assay using cell lysates, Pilaralisib (XL147) does not inhibit mTOR activity toward the physiologic substrate protein eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1; IC50>15 μM). Consistent with its inhibitory activity against purified PI3K proteins, Pilaralisib (XL147) inhibits EGF-induced PIP3production in PC-3 and MCF7 cells in serum-free medium with IC50s of 220 and 347 nM, respectively. The ability of Pilaralisib (XL147) to inhibit phosphorylation of key signaling proteins downstream of PI3K is examined by assessing its effects on EGF-stimulated phosphorylation of AKT and on nonstimulated phosphorylation of S6 in PC-3 cells in serum-free media by cell-based ELISA. Pilaralisib (XL147) inhibits these activities with IC50s of 477 and 776 nM, respectively[1].

体内研究
(In Vivo)

The ability of Pilaralisib (XL147) to inhibit this endogenous phosphorylation of AKT, p70S6K, and S6 is examined following a single oral dose of 10, 30, 100, or 300 mg/kg. The tumors are harvested 4, 24, or 48 hours postdose and homogenized in lysis buffer. Tumor lysates from each animal (n=4) are then pooled for each group and analyzed for levels of total and phosphorylated AKT, p70S6K, and S6 by Western immunoblotting. Administration of Pilaralisib (XL147) causes a dose-dependent decrease in phosphorylation of AKT, p70S6K, and S6 in the tumors, reaching a maximum of 81% inhibition of AKT phosphorylation at 300 mg/kg at 4 hours. The dose-response relationships derived from the 4-hour time point predict 50% inhibition of AKT, p70S6K, and S6 phosphorylation at doses of approximately 100 mg/kg (pAKTT308), 54 mg/kg (pAKTS473), 71 mg/kg (p-p70S6K), and 103 mg/kg (pS6). The inhibition of AKT, p70S6K, and S6 phosphorylation in MCF7 tumors following a 100 mg/kg dose of Pilaralisib (XL147) is maximal at 4 hours, reaching 55% to 75%; however, the level of inhibition decreased to 8% to 45% by 24 hours, and only minimal or no inhibition was evident by 48 hours. Following a 300 mg/kg dose of Pilaralisib (XL147), inhibition is also maximal at 4 hours (65%-81%). However, in contrast with the 100 mg/kg dose, inhibition at 24 hours (51%-78%) is almost comparable with that seen at 4 hours, and partial inhibition (25%-51%) persisted through 48 hours[1].

Clinical Trial
分子量

541.02

性状

Solid

Formula

C25H25ClN6O4S

CAS 号

934526-89-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : ≥ 100 mg/mL(184.84 mM)

*"≥" means soluble, but saturation unknown.

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.8484 mL9.2418 mL18.4836 mL
5 mM0.3697 mL1.8484 mL3.6967 mL
10 mM0.1848 mL0.9242 mL1.8484 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (4.62 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.62 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: 2.5 mg/mL (4.62 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (4.62 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在本网站选购。