LY 294002

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    LY294002 is a potent inhibitor of class I phosphoinositide 3-kinases (PI3Ks) [1, 2]. It is cell permeable and reversible, and selective against p110α, p110β, p110γ and p110δ, which acts on ATP binding site of the catalytic subunit.
    PI3K family is divided into 3 classes: class I, II and III. LY294002 can inhibit 3 out of 4 isoforms of catalytic subunit of class I group. The IC50s for p110α, β andδ are 500 nM, 973 nM and 570 nM [3]. Even though it is less potent than wortmannin, other PI3K inhibitor, but it is more stable in solution. In addition, LY294002 is a reversible inhibitor whereas wortmannin acts irreversibly. [2]
    PI3Ks signal through Akt, activates mTOR and inhibits Bad, leading to cell growth and proliferation. LY294002 potently inactivates PI3K class I catalytic subunit, resulting in induction of apoptosis and suppression of tumor cell growth in vitro and in vivo. [2, 4]
    LY294002 is also a potent autophagy inhibitor by blocking autophagosome formation. [5]
    Quantitative chemoproteomic profiling shows that LY294002 inhibits the BET bromodomain proteins BRD2, BRD3, and BRD4 with IC50 value of 1-2 µM. [6]
    
    [1]Maira et al. (2009). PI3K inhibitors for cancer treatment: where do we stand?. doi:10.1042/BST0370265.
    [2]Vlahos CJ., et al. (1994). A Specific Inhibitor of Phosphatidylinositol 3-Kinase, 2-(4-Morpholinyl)-8-phenyl-4H-l-benzopyran-4-one (LY294002). Journal of Biological Chemistry 269 (7): 5241–5248.
    [3]Chaussade C, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J, 2007, 404(3), 449-58.
    [4]Hu L, et al. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin Cancer Res, 2000, 6(3), 880-6.
    [5]Blommaart EF., et al., (1997). The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243: 240–246.
    [6]Dittmann, A., et al. (2013). The Commonly Used PI3-Kinase Probe LY294002 is an Inhibitor of BET Bromodomains. ACS Chemical Biology: 131210150813004.
- Properties
  - Alternative Name
    
    2-morpholin-4-yl-8-phenylchromen-4-one
    
    CAS Number
    
    154447-36-6
    
    Molecular Formula
    
    C19H17NO3
    
    Molecular Weight
    
    307.34
    
    Appearance
    
    A solid
    
    Purity
    
    99.17%
    
    Solubility
    
    insoluble in H2O; ≥13.55 mg/mL in EtOH; ≥15.37 mg/mL in DMSO
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Liang Yu, Guoqiang Zhou, et al. "Interleukin-8 Regulates the Autophagy and Apoptosis in Gastric Cancer Cells via Regulating PI3K/Akt Signaling Pathway." Dis Markers. 2022 Aug 11;2022:7300987. PMID: 35990250
    2. Baoyi Guan, Jie Gao, et al. "Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway." Evid Based Complement Alternat Med. 2022 Mar 26;2022:7941039. PMID: 35378909
    3. Xuqing Qin, Wenjun He, et al. "Inhibition of Connexin 43 reverses ox-LDL-mediated inhibition of autophagy in VSMC by inhibiting the PI3K/Akt/mTOR signaling pathway." PeerJ. 2022 Mar 16;10:e12969. PMID: 35313522
    4. Yu Pang, Wennan Lin, et al. "Inhibiting Autophagy Pathway of PI3K/AKT/mTOR Promotes Apoptosis in SK-N-SH Cell Model of Alzheimer's Disease." J Healthc Eng. 2022 Feb 8;2022:6069682. PMID: 35178230
    5. Jian Xie, Yunhua Lin, et al. "Human Urinary Kallidinogenase (HUK) Alleviates Myocardial Injury in Rats with Coronary Microembolism Through PI3K/Akt/FoxO1 Signaling Pathway." Research Square. rs-1054881/v1.
    6. Siwei Xia, Zhimin Wang, et al. "Dihydroartemisinin regulates lipid droplet metabolism in hepatic stellate cells by inhibiting lncRNA-H19-induced AMPK signal." Biochem Pharmacol. 2021 Oct;192:114730. PMID: 34400125
    7. YUNCHEN YU, YUYING ZHU, et al. "DL-3-n-butylphthalide protects H9c2 cardiomyoblasts from ischemia/reperfusion injury by regulating HSP70 expression via PI3K/AKT pathway activation." Exp Ther Med. 2021 Sep;22(3):1008. PMID: 34345290
    8. Haibing Zhan, Xingchang Sun, et al. "LncRNA MEG3 Involved in NiO NPs-Induced Pulmonary Fibrosis via Regulating TGF-β1-Mediated PI3K/AKT Pathway." Toxicol Sci. 2021 Jul 16;182(1):120-131. PMID: 33895847
    9. Chu-di Zhang, Yi-Long Wang, et al. "A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway." Transl Oncol. 2021 Jul;14(7):101091. PMID: 33848808
    10. Chang Shu, Shumei Han, et al. "Integrin β1 regulates proliferation, apoptosis, and migration of trophoblasts through activation of phosphoinositide 3 kinase/protein kinase B signaling." J Obstet Gynaecol Res. 2021 Jul;47(7):2406-2416. PMID: 33843127
    11. Qiang Li, Dongmei Yu, et al. "TIPE3 promotes non-small cell lung cancer progression via the protein kinase B/extracellular signal-regulated kinase 1/2-glycogen synthase kinase 3β-β-catenin/Snail axis." Transl Lung Cancer Res. 2021 Feb;10(2):936-954. PMID: 33718034
    12. Zichao Wang, Lijun Sun, et al. "Lycium ruthenicum Murray anthocyanins effectively inhibit α-glucosidase activity and alleviate insulin resistance." Food Bioscience.Volume 41, June 2021, 100949.
    13. Zhi-Qing Chen, You Zhou, et al. "Breviscapine Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Rats After Coronary Microembolization by Activating the PI3K/Akt/GSK-3β Signaling Pathway." Drug Des Devel Ther. 2021 Feb 25;15:843-855. PMID: 33658766
    14. Jiajia Lu, Zhibin Zhou, et al. "Tumour necrosis factor‐α promotes BMHSC differentiation by increasing P2X7 receptor in oestrogen‐deficient osteoporosis." J Cell Mol Med. 2020 Nov 9. PMID: 33169524
    15. Dan Li, Yongli Yang, et al. "Effect of young apple (Malus domestica Borkh. cv. Red Fuji) polyphenols on alleviating insulin resistance." Food Bioscience 36 (2020) 100637.
    16. Ruirui Lu, Junqi Chen, et al. "Protective role of Astragaloside IV in chronic glomerulonephritis by activating autophagy through PI3K /AKT /AS160 pathway." Phytotherapy Research. 2020;1–13.
    17. Fang Y, Ou S, et al. "Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease." PeerJ. 2020;8:e9308. PMID: 32551202
    18. Wang F, Zhang J, et al. "The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus." Immunobiology. 2020;225(3):151933. PMID: 32201095
    19. Wang K, Peng S, et al. "Naringin inhibits autophagy mediated by PI3K-Akt-mTOR pathway to ameliorate endothelial cell dysfunction induced by high glucose/high fat stress." Eur J Pharmacol. 2020;874:173003. PMID: 32045600
    20. Yue J, Zhao X. "GPR174 suppression attenuates retinopathy in angiotensin II (Ang II)-treated mice by reducing inflammation via PI3K/AKT signaling." Biomed Pharmacother. 2020;122:109701. PMID: 31918274
    21. Xuyang Zhao, Yadong Ma, et al. "mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma." bioRxiv. 2020 January 13.
    22. Xin M, Jin X, et al. "Dipeptidyl peptidase-4 inhibition prevents vascular aging in mice under chronic stress: Modulation of oxidative stress and inflammation." Chem Biol Interact. 2019 Oct 2:108842. PMID: 31586451
    23. Dª María Castejón Griñán. "MELANOCORTIN 1 RECEPTOR AS REGULATOR OF PROTECTIVE RESPONSES AGAINST OXIDATIVE STRESS AND UVR-INDUCED DNA DAMAGE." UNIVERSIDAD DE MURCIA. 2019.
    24. Guo LT, Wang SQ, et al."Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway." J Neuroinflammation. 2019 May 8;16(1):95. PMID: 31068207
    25. Liu J, Li J, et al. "H(2)S attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism." Exp Ther Med. 2019 May;17(5):4064-4072. PMID: 31007743
    26. Huang SZ, Wei MN, et al. "Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma." Front Oncol. 2019 Mar 15;9:150. PMID: 30931258
    27. Zheng L, Guo Q, et al. "Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells." J Hematol Oncol. 2019 Mar 4;12(1):23. PMID: 30832689
    28. Gao L, Guo Q, et al. "MiR-873/PD-L1 axis regulates the stemness of breast cancer cells." EBioMedicine. 2019 Feb 22. pii: S2352-3964(19)30112-4. PMID: 30803931
    29. Zhang R, Ma Z, et al. "Baicalin exerts antidepressant effects through Akt/FOXG1 pathway promoting neuronal differentiation and survival." Life Sci. 2019 Mar 15;221:241-248. PMID: 30794828
    30. Zhang H, Wei Q, et al. "Semaphorin 4A acts in a feed-forward loop with NF-κB pathway to exacerbate catabolic effect of IL-1β on chondrocytes." Int Immunopharmacol. 2019 Apr;69:88-94. PMID: 30685700
    31. Cui W, Leng B, et al. "Klotho protein inhibits H2O2-induced oxidative injury in endothelial Cells via regulation of PI3K/Akt/Nrf2/HO-1 Pathways." Can J Physiol Pharmacol. 2018 Dec 21. PMID: 30576222
    32. Liu MF, Xue Y, et al. "Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson's Disease." Front Neurosci. 2018 Nov 15;12:835. PMID: 30524223
    33. Cui W, Leng B, et al. "Suppression of Apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) by Klotho Protein is Associated with Reduced Endoplasmic Reticulum Oxidative Stress and Activation of the PI3K/AKT Pathway."Med Sci Monit. 2018 Nov 24;24:8489-8499. PMID: 30471224
    34. Chu D, Zhang Z. "Trichosanthis Pericarpium Aqueous Extract Protects H9c2 Cardiomyocytes from Hypoxia/Reoxygenation Injury by Regulating PI3K/Akt/NO Pathway." Molecules. 2018 Sep 20;23(10). pii: E2409. PMID: 30241309
    35. YugenShia,JieYina,et al. "Targeted regulation of sympathetic activity in paraventricular nucleus reduces inducible ventricular arrhythmias in rats after myocardial infarction." Journal of Cardiology Available online 4 July 2018.
    36. MXinwei Feng1, Junfeng Lu2, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
    37. He GR, Lin XK, et al. "Dexmedetomidine impairs Pglycoprotein mediated efflux function in L02 cells via the adenosine 5'monophosphate activated protein kinase/nuclear factor κB pathway." Mol Med Rep.2018 Apr;17(4):5049-5056. PMID: 29393492
    38. Lixing X, Zhouye J, et al."Saikosaponin-d-mediated downregulation of neurogenesis results in cognitive dysfunction by inhibiting Akt/Foxg-1 pathwayin mice." Toxicol Lett. 2017 Nov 9.pii: S0378-4274(17)31457-1. PMID: 29129800
    39. Ha SD, Cho W, et al. "HDAC8 Prevents Anthrax Lethal Toxin-induced Cell Cycle Arrest through Silencing PTEN in Human Monocytic THP-1 Cells." Toxins (Basel).2017 May 16;9(5). pii: E162. PMID: 28509866
    40. Smich, Joanna. "Radiation response and PI3K/mTOR targeting in canine melanoma." The University of Guelph.2016.09.06
    41. Zheng, Lufeng, et al. "The 3′ UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1." Breast cancer research and treatment (2015): 1-14. PMID: 25701119

LY 294002

Background

We Also Recommend

Nintedanib (BIBF 1120)

PD 173074

TAE684 (NVP-TAE684)