LY294002 / Eli Lilly 
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  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models. (Pubmed Central) -  Apr 12, 2022   
    Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002...Enhancement of glycolysis might be another factor of hirsutine showing its effects on glycemic control. Collectively, it was uncovered that hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  Cinnamaldehyde Downregulation of Sept9 Inhibits Glioma Progression through Suppressing Hif-1α via the Pi3k/Akt Signaling Pathway. (Pubmed Central) -  Apr 8, 2022   
    Pi3k inhibitor (LY294002) was used for interfering with cells, and the results found CA to demonstrate a similar effect...It is suggested that the mechanism of Sept9 under hypoxia regulation can be realized through the Pi3k/Akt pathway. This study proves for the first time that CA is an effective drug for inhibiting the proliferation of glioma through Sept9 and reveals Sept9 to be related to the Pi3k/Akt pathway in terms of tumor microenvironment, providing a molecular basis for the further study of CA in glioma treatment.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  SET8，a novel regulator to ameliorate vascular calcification via activating PI3K/Akt mediated anti-apoptotic effects. (Pubmed Central) -  Apr 5, 2022   
    Mechanistically, the PI3K/Akt pathway was mediated by SET8, and inhibition of the PI3K/Akt signaling pathway by administering LY294002 or transfecting the Akt phosphorylation-inactivated mutation plasmid increased apoptosis and calcification...Furthermore, exogenous overexpression of SET8 could reverse the effect of PI3K/Akt inhibition on the apoptosis and calcification of VSMCs. In summary, our researches suggested that SET8 overexpression ameliorated high phosphorus induced calcification of vascular smooth muscle cells via activating PI3K/Akt mediated anti-apoptotic effects.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Saikosaponin-D Mitigates Oxidation in SH-SY5Y Cells Stimulated by Glutamate Through Activation of Nrf2 Pathway: Involvement of PI3K. (Pubmed Central) -  Apr 5, 2022   
    Furthermore, addition of LY294002, a selective inhibitor of PI3K (phosphatidylinositol 3 kinase), blocked saikosaponin-D-caused Nrf2 nuclear translocation and reversed the protection of saikosaponin-D against glutamate in SH-SY5Y cells...Taken together, our results indicated that saikosaponin-D enhanced cellular antioxidant capacity through not only intrinsic free radical-scavenging activity but also induction of endogenous antioxidant enzyme activities and HO-1 expression mediated, at least in part, by activating PI3K and subsequently Nrf2 nuclear translocation, thereby protecting the SH-SY5Y cells from glutamate-induced oxidative cytotoxicity. In concert, these data raise the possibility that saikosaponin-D may be an attractive candidate for prevention and treatment of AD and other diseases related to oxidation in the future.
  • ||||||||||  RSL3 / Stanford University
    Preclinical, Journal:  Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis. (Pubmed Central) -  Apr 5, 2022   
    On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent...However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Quercetin inhibits AQP1 translocation in high-glucose-cultured SRA01/04 cells through PI3K/Akt/mTOR Pathway. (Pubmed Central) -  Apr 1, 2022   
    Quercetin significantly decreased the AQP1 elevation and prevented the change of AQP1 location through inhibiting the activation of the PI3K/Akt/mTOR signaling in high-glucose-cultured SRA01/04 cells, which might have the preventable and inhibitory effects on the early development of diabetic cataract. The specific pathophysiological role of quercetin still needs to be verified.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, Cancer stem cells:  microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway. (Pubmed Central) -  Apr 1, 2022   
    Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis...Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.
  • ||||||||||  LY294002 / Eli Lilly, XAV-939 / Novartis
    Journal:  Dec1 Deficiency Ameliorates Pulmonary Fibrosis Through the PI3K/AKT/GSK-3β/β-Catenin Integrated Signaling Pathway. (Pubmed Central) -  Apr 1, 2022   
    Herein, we aimed to explore DEC1 expression in IPF and bleomycin (BLM)-induced PF in mice and the mechanisms underlying the fibrogenic effect of DEC1 in PF in vivo and in vitro by Dec1-knockout (Dec1 ) mice, knockdown and overexpression of DEC1 in alveolar epithelial cells (A549 cells)...Moreover, the PI3K/AKT and Wnt/β-catenin signaling inhibitors, LY294002 and XAV-939, ameliorated BLM-meditated PF in vivo and relieved EMT in vivo and in vitro...Our findings indicated that during PF progression, DEC1 played a key role in EMT via the PI3K/AKT/GSK-3β/β-catenin integrated signaling pathway. Consequently, targeting DEC1 may be a potential novel therapeutic approach for IPF.
  • ||||||||||  simvastatin / Generic mfg.
    Journal:  Simvastatin treatment promotes proliferation of human dental pulp stem cells via modulating PI3K/AKT/miR-9/KLF5 signalling pathway. (Pubmed Central) -  Mar 29, 2022   
    Finally, the level of KLF5 in cells was much lower following the transfection with miR-9 and KLF5 siRNA, and the level of AKT mRNA in cells was significantly inhibited after transfection with AKT siRNA than control. These findings suggested simvastatin could promote the proliferation of pulp stem cells, possibly by suppressing the expression of miR-9 via activating the PI3K/AKT signalling pathway, and the downregulation of miR-9 upregulated the expression of its target gene, KLF5, which is directly responsible for the enhanced proliferation of pulp stem cells.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway. (Pubmed Central) -  Mar 29, 2022   
    It was further demonstrated that B7‑H3 ablation significantly downregulated phosphorylated AKT/protein kinase B expression, and SIRT1 expression was substantially suppressed by the PI3K‑specific inhibitor, LY294002. Taken together, the findings of the present study revealed that B7‑H3‑induced signaling upregulates SIRT1 expression via the PI3K/AKT pathway to promote EMT activation that is associated with metastasis in NSCLC.
  • ||||||||||  metformin / Generic mfg.
    Preclinical, Journal, IO biomarker:  Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo. (Pubmed Central) -  Mar 26, 2022   
    In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.