LY294002

生物活性

LY294002是一种广谱的PI3K抑制剂，对PI3Kα/δ/β的IC50分别为0.5 μM/0.57 μM/0.97 μM。LY294002 也可以抑制 CK2 的活性，IC50 为 98 nM。LY294002 还是一种竞争性 DNA-PK 抑制剂，可逆结合 DNA-PK 的激酶结构域，IC50 为 1.4 μM。LY294002也能够抑制自噬体的形成。LY294002使Akt/PKB失活,因此抑制细胞增殖和诱导细胞凋亡。 LY294002作用于结肠癌细胞系，使磷酸化Akt (Ser473)的表达下降， 明显抑制生长和诱导凋亡。LY294002作用于肿瘤细胞，诱导明显的核固缩和减少细胞质体积。LY294002 是一种凋亡 (apoptosis) 激活剂。

使用AbMole产品发表的文献

• J Cell Physiol. 2023 Apr 3.

  Bisphenol A aggravate selenium deficiency‐induced apoptosis via miR‐215‐3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial

• J Ethnopharmacol. 2023 Apr 6;305:116062.

  Paiteling induces apoptosis of cervical cancer cells by down-regulation of the E6/E7-Pi3k/Akt pathway: A network pharmacology

• Platelets. 2023 Feb 22;2173505.

  Alantolactone induces platelet apoptosis by activating the Akt pathway

• Toxicology Research. 2023 May 14.

  Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway

• J Chin Med Univ. 2023 Jan.

  Brain-derived neurotrophic factor promotes regenerative repair of rat sciatic nerve through PI3K/Akt signaling pathway

• Journal of China Medical University. 2023 Feb;Vol. 52 Issue 1, p51-56.

  Brain-derived neurotrophic factor promotes regeneration and repair of rat sciatic nerve through PI3K/Akt signaling pathway

• Cell Biol Toxicol. 2022 Apr;38(2):291-310.

  Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage

• Front Pharmacol. 2022 Feb 21;13:828061.

  Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT–IKK/STAT3 Axis

• Mol Carcinog. 2022 Sep 4;61(9):839-850.

  HIF‐1α‐regulated stanniocalcin‐1 mediates gemcitabine resistance in pancreatic ductal adenocarcinoma via PI3K/AKT signaling pathway

• Nutr Cancer. 2022;74(10):3747-3760.

  Fucoxanthin Inactivates the PI3K/Akt Signaling Pathway to Mediate Malignant Biological Behaviors of Non-Small Cell Lung Cancer

• Iran J Basic Med Sci. 2022 May;25(5):635-642.

  Transient receptor potential vanilloid type-1 regulates periodontal disease damage via the PI3K/AKT signaling pathway

• Environ Pollut. 2021 Feb 1;270:116051.

  Bisphenol AF induces apoptosis via estrogen receptor beta (ERβ) and ROS-ASK1-JNK MAPK pathway in human granulosa cell line KGN

• Front Cell Dev Biol. 2021 Aug 6;9:649656.

  PI3K Plays an Essential Role in Planarian Regeneration and Tissue Maintenance

• Front Pharmacol. 2021 Sep 23;12:749930.

  Carbamazepine Induces Platelet Apoptosis and Thrombocytopenia Through Protein Kinase A

• Ecotoxicol Environ Saf. 2021 Jan 15;208:111429.

  Bisphenol A induces apoptosis through GPER-dependent activation of the ROS/Ca 2+-ASK1-JNK pathway in human granulosa cell line KGN

• Am J Transl Res. 2021 May 15;13(5):4040-4054.

  Guanosine ameliorates positive symptoms of schizophrenia via modulating 5-HT 1A and 5-HT 2A receptors

• Ann Transl Med. 2021 Jul;9(13):1087.

  Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation

• Curr Pharm Des. 2021;27(29):3244-3250.

  MiR-92a-3p Promotes the Malignant Progression of Hepatocellular Carcinoma by Mediating the PI3K/AKT/mTOR Signaling Pathway

• J Biomed Sci. 2020 Jan 13;27(1):5.

  Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells.

• Onco Targets Ther. 2020 Jul 31;13:7585-7598.

  JuBei Oral Liquid Induces Mitochondria-Mediated Apoptosis in NSCLC Cells

• Eur J Pharmacol. 2020 Jan 15;867:172811.

  Triptolide inhibits PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

• Biomed Res Int. 2020 Jun 20;2020:9243681.

  Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant A549/DDP Cells via the AKT-mTOR-c-Myc Signaling Pathway

• J Int Med Res. 2020 Aug;48(8):300060520946169.

  Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells

• Front Immunol. 2019 Apr 26;10:913.

  IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth.

• Clin Sci (Lond). 2019 May 21;133(10):1167-1184.

  Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis.

• Gynecol Oncol. 2019 Jun;153(3):661-669.

  Chloride channel-3 is required for efficient tumour cell migration and invasion in human cervical squamous cell carcinoma.

• Cell Mol Neurobiol. 2019 Mar;39(2):301-319.

  Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 Signal Transduction Pathway.

• Placenta. 2019 Nov;87:38-45.

  Reduced ELABELA expression attenuates trophoblast invasion through the PI3K/AKT/mTOR pathway in early onset preeclampsia.

• Apoptosis. 2018 May 18.

  Down-regulating IL-6/GP130 targets improved the anti-tumor effects of 5-fluorouracil in colon cancer.

• J Cell Physiol. 2018 Nov 19.

  Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction.

• Exp Eye Res. 2018 Nov;176:10-19.

  Rapamycin mediates mTOR signaling in reactive astrocytes and reduces retinal ganglion cell loss.

• BMC Genomics. 2017 Sep 11;18(1):714.

  The dynamic landscape of gene regulation during Bombyx mori oogenesis.

• Mol Immunol. 2017 Jul;87:132-140.

  IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway

• Int Immunopharmacol. 2017 Dec;53:149-157.

  Oxymatrine protects against DSS-induced colitis via inhibiting the PI3K/ AKT signaling pathway

• Mol Med Rep. 2017 Oct;16(4):5699-5705.

  Ca2+/Mg2+ homeostasis‑related TRPM7 channel mediates chondrocyte hypertrophy via regulation of the PI3K‑Akt signaling pathway

• Oncotarget. 2016 Feb 22.

  Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo.

• Oncol Res. 2016;24(5):287-293.

  Knockdown of Rap1b Enhances Apoptosis and Autophagy in Gastric Cancer Cells via the PI3K/Akt/mTOR Pathway

• Biochem Pharmacol. 2015 Aug 15;323-36.

  Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

• Int Immunopharmacol. 2015 Dec;583-90.

  DGAEE, a newly synthesized derivative of glycyrrhetinic acid, potently attenuates mouse septic shock via its main metabolite DGA in an IL-10-dependent manner.

• Acta Universitatis Medicinalis Anhui. 2015 Nov;50(11):1629-1633.

  Protective Effects of Astragaloside IV on High Insulin Induced Human Mesangial Cells Injury and Its Mechanisms

• 2015 Apr.

  THE MECHANOBIOLOGICAL MECHANISMS OF CAVEOLAE/CAVEOLIN-1 IN LOW SHEAR STRESS-INDUCED BREAST CARCINOMA CELL MIGRATION AND INVASION

产品使用成果展示

	数据来源	J Cell Physiol (2018). Figure 3. LY294002 (AbMole Bioscience Inc.)
	方法	injected
	细胞系/动物模型	rats
	浓度
	处理时间	72 h
	实验结果	The LY294002 group had increased infarct size (p < 0.05); while no such significantdifference was found in the ANXA3-shRNA + LY294002 group

	数据来源	Experimental Eye Research (2018). Figure 3. LY294002 (Abmole Bioscience, Houston, TX, USA)
	方法	Western blot
	细胞系/动物模型	ONH astrocytes
	浓度	50 μM
	处理时间	1 h
	实验结果	PD98059 did not significantly reduce the level of p-S6 kinase phosphorylation, but LY294002 showed a robust blockade of its phosphorylation.

	数据来源	Journal of Nanchang University (2017). Figure 5. LY294002 (Abmole Bioscience)
	方法	Western Blotting
	细胞系/动物模型	A549 Cell
	浓度	20 μM
	处理时间	24 h
	实验结果	Western Blotting检测结果显示，LY294002处理组的PI3K，p-AKT的表达比对照组显著降低（均P < 0.05）。

	数据来源	Journal of Nanchang University (2017). Figure 4. LY294002 (Abmole Bioscience)
	方法	Western Blotting
	细胞系/动物模型	A549 Cell
	浓度	20 μM
	处理时间	24 h
	实验结果	Western Blotting检测结果显示，LY294002处理的A549细胞中Beclin-1蛋白表达和LC3B（Ⅱ／Ⅰ）比率比对照组显著降低（均P < 0.05）。

	数据来源	Journal of Nanchang University (2017). Figure 3. LY294002 (Abmole Bioscience)
	方法	Wound Healing assay
	细胞系/动物模型	A549 Cell
	浓度	20 μM
	处理时间	24 h
	实验结果	Wound Healing实验结果显示，LY294002处理组细胞24h迁徙率为（22.4±2.6）%，显著低于对照组（39.1±3.2）%（P < 0.05）。

	数据来源	Journal of Nanchang University (2017). Figure 2. LY294002 (Abmole Bioscience)
	方法	Transwell assay
	细胞系/动物模型	A549 Cell
	浓度	20 μM
	处理时间	24 h
	实验结果	Transwell侵袭实验结果显示，LY294002处理组侵出小室的细胞数为（95±7）个/膜，显著低于对照组（130±16）个/膜（P < 0.05）。

	数据来源	Int Immunopharmacol. (2017). Figure 6. LY294002 (Abmole Bioscience, Hong Kong, China)
	方法	qRT-PCR
	细胞系/动物模型	Th1 and Th17 cells
	浓度	50 mg/kg
	处理时间
	实验结果	Western blot and quantitative RT-PCR analysis revealed that OMT and LY294002 treatment resulted in dramatic reduction of Tbet and ROR-γt (Fig. 6A and B).

	数据来源	Int Immunopharmacol. (2017). Figure 5. LY294002 (Abmole Bioscience, Hong Kong, China)
	方法	Flow cytometry
	细胞系/动物模型	CD4+ T cells
	浓度	50 mg/kg
	处理时间
	实验结果	OMT and LY294002 reduced the percentage of Th1-polarized and Th17-polarized CD4+ T cells (Fig. 5A and B).

	数据来源	Int Immunopharmacol. (2017). Figure 2. LY294002 (Abmole Bioscience, Hong Kong, China)
	方法	Western blot
	细胞系/动物模型	Specific pathogen-free (SPF) male BALB/c mice
	浓度	50 mg/kg
	处理时间
	实验结果	Whereas, OMT and LY294002 triggered apoptosis by activated cleaved-caspase3 and cleaved-caspase9 and lowed the expression of Bcl-2 and Bad in colonic tissues (Figs. 2A, B and 3).

	数据来源	Int Immunopharmacol. (2017). Figure 1. LY294002 (Abmole Bioscience, Hong Kong, China)
	方法	Evaluate DAI
	细胞系/动物模型	Specific pathogen-free (SPF) male BALB/c mice
	浓度	50 mg/kg
	处理时间
	实验结果	Meanwhile, the DAI score and histological score, reflecting the severity of UC, also decreased obviously in the OMT and LY294002 treated groups (Fig. 1E and F).

	数据来源	BMC Genomics (2017). Additional file 7. LY294002 (Abmole Bioscience, USA)
	方法	qRT-PCR
	细胞系/动物模型	pupa abdomen
	浓度
	处理时间	48 h
	实验结果	We performed injection experiments involving several inhibitors of the insulin signaling pathway. It was observed that the development of follicles was clearly delayed and the follicles showed abnormalities (Additional file 7), and the expressions of marker genes, like Cyp18a1 and early chorion gene, were up-regulated at choriogenic stages.

	数据来源	Oncology research (2016). Figure 4. LY294002 (Abmole Bioscience, Shanghai, China)
	方法	MTT assay
	细胞系/动物模型	MKN-28 and SGC-7901 cells
	浓度	200 nM
	处理时间	12 h
	实验结果	The Rap1b silencinginduced enhancement of apoptosis and autophagy in MKN-28 and SGC-7901 cells was enhanced by LY294002 but was blocked by IGF-1 treatment (Fig. 4B and C).

	数据来源	Mol Immunol (2017) . Figure 5. LY294002 (Abmole Bioscience, USA)
	方法	LC3 in SMMC-7721 and Huh-7 cells treated with IL-37 (100 ng/ml) or LY294002 (20 μmol/l).
	细胞系/动物模型	SMMC-7721 and Huh-7 cells
	浓度	20 μmol/l
	处理时间
	实验结果	The expression of p-AKT and p-mTOR was decreased and the LC3-II/LC3-I ratio was increased in IL-37 treated LY294002-treated SMMC-7721 and Huh-7 cells. The mediated effects of IL-37 on autophagy were similar to those of the inhibitor LY294002 (Fig. 5D).

	数据来源	Biochem Pharmacol (2015). LY294002, Figure 5. (Abmole Bioscience Kowloon, Hong Kong, China)
	方法	Western blot
	细胞系/动物模型	CD4+ T cells
	浓度	20 mM
	处理时间	24 h
	实验结果	Fig. 5B showed that PI3K inhibitor LY294002 markedly suppressed p70S6K and RPS6 phosphorylation.

	数据来源	Oncotarget (2016). Figure 11. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
	方法	western blot
	细胞系/动物模型	MDA-MB-231 cells
	浓度	PI3K (10 µM LY294002), Akt (10 µM MK-2206) or mTOR (10 µM rapamycin)
	处理时间	1h
	实验结果	As shown in Figure 11. Pretreating MDA-MB-231 cells with the specific inhibitors of PI3K (10 µM LY294002), Akt (10 µM MK-2206) and mTOR (10 µM rapamycin) completely abolished the LSS-induced MT1-MMP expression, indicating that the PI3K/Akt/mTOR pathway is required for LSS-induced MT1-MMP expression.

	数据来源	Oncotarget (2016). Figure 1. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
	方法	Cell motility assay
	细胞系/动物模型	MDA-MB-231 cells
	浓度	PI3K (10 μM LY294002), Akt (20 μM MK-2206), mTOR (10 μM rapamycin, Rap), FAK (10 μM PF573228) or Src (10 μM PP2)
	处理时间	1h
	实验结果	"Notably, inhibitors of PI3K (LY294002), Akt (MK-2206) and mTOR (rapamycin) markedly decreased the LSS-induced wound closure activity. However, pretreatment with inhibitors of FAK (PF573228) and Src (PP2) has no effect on the LSS-induced cell motility (Figure 1B). It is suggested that PI3K, Akt and mTOR might be participated LSS-induced cell motility in an FAK and Src-independent manner. "

	数据来源	Biochemical Pharmacology (2015). Figure 7. LY294002, MK-2206 and GSK1120212 were gifts from Abmole Bioscience (Kowloon, Hong Kong).
	方法	Western blot
	细胞系/动物模型	Purified CD4+ T cells
	浓度	20 mM LY294002, 10 mM MK-2206 as well as 10 mM GSK1120212
	处理时间	3 h
	实验结果	Arctigenin could inhibit mTORC1 activation via a way independent of PI3K/AKT and ERK.

	数据来源	International Immunopharmacology (2015). Figure 7. LY294002 (an inhibitor of GSK3 phosphorylation) was purchased from Abmole Bioscience (Kowloon, Hong Kong)
	方法	(A) Level of IL-10 was detected by using ELISA assay. (B) Levels of p-GSK3β (Ser9) and GAPDH were detected by using Western blot assay.
	细胞系/动物模型	RAW 264.7 cells
	浓度	5 µM
	处理时间	24 hours
	实验结果	LY294002 (5 μM) obviously diminished DGA-mediated IL-10 expression in LPS-stimulated RAW 264.7 cells

实验参考

体外实验*
细胞系	DLD-1, LoVo
方法	Cells were seeded at a density of 1.0×105 cells/well in a 96-well plate and incubated in completely fresh medium containing 0–50µM LY294002 for 24 h for proliferation assay. Western blot analysis of the level of Akt phosphorylation in DLD-1 and LoVo cells in 6-well plate.
浓度	10, 20, 50 µM
处理时间	24 hours

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	Both DLD-1 and LoVo cancer cells models in SCID 6-week-old female mice
配制	Dissolved in DMSO
剂量	2.0 ng/ml/kg
给药处理	From days 20–40, i.v. or i.p. injection everyday

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	307.34
分子式	C19H17NO3
CAS号	154447-36-6
溶解性（25°C）	DMSO 32 mg/mL Ethanol 20 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	3.2537 mL	16.2686 mL	32.5373 mL
5 mM	0.6507 mL	3.2537 mL	6.5075 mL
10 mM	0.3254 mL	1.6269 mL	3.2537 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Lianguzova MS, et al. Cell Biol Int. Phosphoinositide 3-kinase inhibitor LY294002 but not serum withdrawal suppresses proliferation of murine embryonic stem cells.

[2] Gharbi SI, et al. Biochem J. Exploring the specificity of the PI3K family inhibitor LY294002.