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PI-103

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Chemical Structure| 371935-74-9 同义名 : -
CAS号 : 371935-74-9
货号 : A344838
分子式 : C19H16N4O3
纯度 : 99%+
分子量 : 348.355
MDL号 : MFCD11983145
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(25.84 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • p110γ

    p110γ, IC50:15 nM

  • p110β

    p110β, IC50:3 nM

  • p110α

    p110α, IC50:2 nM

  • p110δ

    p110δ, IC50:3 nM
描述 PI3K/AKT/mTOR pathway directly relates to cellular quiescence, proliferation, cancer, and longevity. There are eight PI3 kinases have been identified as classes IA, 1B, II, and III based on the sequence homology and substrate preference. Among them, class IA PI3K is composed of a heterodimer consisting of a 110 kDa catalytic subunit (p110α, p110β and p110δ) and an 85 kDa regulatory subunit [2]. PI-103 is a dual inhibitor of Class IA PI3Ks (p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM determined using a scintillation proximity assay, respectively) and mTOR (IC50=30 nM), with less potent to DNA-PK (IC50=23 nM) [1]. PI-103 is usually used in ACUTE LYMPHOBLASTIC LEUKEMIA study. It can inhibit PI3K/Akt and mTORC1 activity in MOLM14, OCI-AML3 and MV4-11 leukemic cell lines, which have constitutive activation of PI3K/Akt (p-Akt Ser 473 and p-FOXO3a Thr32), mTORC1 (p-P70S6K Thr389) signaling pathways, with no inhibition on ERK/MAPK (p-p42/44 ERK/MAPK Thr202/Tyr204). In AML blast cells, PI-103 inhibits both constitutive and growth factor-induced PI3K/Akt and mTORC1 activation, reverses the positive feedback of mTORC1 inhibition on PI3K/Akt and induces significant apoptosis [3]. In glioma, PI‑103 induces autophagy and promotes cell survival by inhibiting mTOR activity. Conversely, PI‑103 can lead to apoptosis by combining with autophagy inhibitors like 3-ma or bafilomycin A1 [4].
作用机制 PI-103 acts as an ATP-competitive inhibitor of PI3K (Class IA). [5]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
518A2 0.01–10 μM Cell Viability Assay 72 h inhibits cell viability dose dependently 21048785
518A2 0.001–1 μM Function Assay 24 h suppresses phosphorylation of phosphatidyl inositol 3-kinase downstream targets 21048785
A549 0.25/0.5/1 μM Function Assay 24 h inhibits Akt phosphorylation slightly 24351425
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.87mL

0.57mL

0.29mL

14.35mL

2.87mL

1.44mL

28.71mL

5.74mL

2.87mL
参考文献

[1]Raynaud FI, Eccles SA, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther. 2009 Jul;8(7):1725-38.

[2]Zhao HF, Wang J, et al. Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development. Mol Cancer. 2017 Jun 7;16(1):100.

[3]Park S, Chapuis N, et al. PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia. 2008 Sep;22(9):1698-706.

[4]Fan QW, Weiss WA, et al. Autophagy and Akt promote survival in glioma. Autophagy. 2011 May;7(5):536-8. Epub 2011 May 1.