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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)
Free Sample (0.1-0.5mg)电议
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议

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。
Cas No.934526-89-3
别名2-氨基-N-[3-[N-[3-[(2-氯-5-甲氧基苯基)氨基]喹喔啉-2-基]氨基磺酰基]苯基]-2-甲基丙酰胺,XL-147; SAR245408
Canonical SMILESCC(C)(N)C(NC1=CC=CC(S(=O)(NC2=NC3=CC=CC=C3N=C2NC4=CC(OC)=CC=C4Cl)=O)=C1)=O
分子式C25H25ClN6O4S
分子量541.02
溶解度DMSO: ≥ 100 mg/mL (184.84 mM); Water:< 0.1 mg/mL (insoluble)
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

Pilaralisib (XL147; SAR245408) is a potent and highly selective class I PI3Ks inhibitor with IC50s of 39 nM, 383 nM, 23 nM and 36 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. 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)

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 IC50 value of 383 nM. The IC50 value 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; IC50 value of ~7.0 M) and the PI3K-related DNA-dependent protein kinase (DNA-PK; IC50 value 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 PIP3 production 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].

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].

[1]. Foster P, et al. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models. Mol Cancer Ther. 2015 Apr;14(4):931-40.