LY294002 / Eli Lilly 
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  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Involvement of PAR2 in platelet-derived growth factor receptor-α-positive cell proliferation in the colon of diabetic mice. (Pubmed Central) -  Mar 23, 2022   
    2-F-L-a also reduced PI3K, Akt, and p-Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα cells through the PI3K/Akt signaling pathway in the colon of STZ-induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Fluorometholone inhibits high glucose-induced cellular senescence in human retinal endothelial cells. (Pubmed Central) -  Mar 23, 2022   
    Lastly, the protective effects of FML against high glucose-induced cellular senescence in HRECs were abolished by the co-treatment of the PI3K/Akt signaling inhibitor LY294002, suggesting the involvement of this pathway. Taken together, these data revealed that FML-inhibited high glucose-induced cellular senescence mediated by Akt in HERCs, suggesting a novel molecular mechanism of FML.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Inhibition of PI3K/AKT/mTOR Signalling Pathway Activates Autophagy and Suppresses Peritoneal Fibrosis in the Process of Peritoneal Dialysis. (Pubmed Central) -  Mar 23, 2022   
    In this experiment, a high-glucose (HG)-induced peritoneal fibrosis rat model was successfully established via intraperitoneal injection of HG peritoneal dialysate, and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the mechanistic target of rapamycin (mTOR) inhibitor rapamycin were used to treat peritoneal fibrosis rats...The current data indicated that inhibition of PI3K/AKT/mTOR signalling pathway activated autophagy and suppressed PF in the process of PD. Therefore, intervention in this signalling pathway may become a research goal for the prevention and treatment of PF, which has important clinical significance.
  • ||||||||||  fasudil / Generic mfg.
    Journal:  Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway. (Pubmed Central) -  Mar 23, 2022   
    As for reinnervation, Neurofilament-200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.
  • ||||||||||  Procoralan (ivabradine) / Amgen, Servier, Ono Pharma
    PROTECTIVE EFFECTS OF IVABRADINE ON H9C2 MYOCARDIAL CELLS INDUCED BY ISCHEMIA/REPERFUSION INJURY ([VIRTUAL]) -  Mar 23, 2022 - Abstract #SCCM2022SCCM_2405;    
    Ivabradine may protect H9c2 cardiomyocytes against I/R injury by reducing apoptosis and oxidative stress via activation of the PI3K/Akt/mTOR signaling pathway. The Results of the present study indicate the potential therapeutic benefits of ivabradine in the treatment of myocardial I/R injury.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  Protection of Human Lens Epithelial Cells from Oxidative Stress Damage and Cell Apoptosis by KGF-2 through the Akt/Nrf2/HO-1 Pathway. (Pubmed Central) -  Mar 18, 2022   
    LY294002, the phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor, abolished KGF-2's effect to some extent, demonstrating that KGF-2 protected HLECs via the PI3K/Akt pathway...Furthermore, as revealed by lens organ culture assays, KGF-2 treatment decreased HO-induced lens opacity in a concentration-dependent manner. As demonstrated by these data, KGF-2 resisted HO-mediated apoptosis and oxidative stress in HLECs through Nrf2/HO-1 and PI3K/Akt pathways, suggesting a potential protective effect against the formation of cataracts.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens. (Pubmed Central) -  Mar 17, 2022   
    In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization...The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine...In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.
  • ||||||||||  AiTan (rivoceranib) / HLB Bio Group, LY294002 / Eli Lilly
    Journal:  PAQR4 promotes the development of hepatocellular carcinoma by activating PI3K/AKT pathway. (Pubmed Central) -  Mar 17, 2022   
    In tumor xenograft model, knockdown of PAQR4 suppressed tumor growth in vivo, while PAQR4 overexpression promoted tumor growth. Collectively, our data suggest that PAQR4 has a tumorigenic effect on HCC progression by activating PI3K/AKT pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Cross-regulation of notch/AKT and serum/glucocorticoid regulated kinase 1 (SGK1) in IL-4-stimulated human macrophages. (Pubmed Central) -  Mar 16, 2022   
    To dissect the signaling pathway leading to SGK1 upregulation, we pretreated THP-1-derived macrophages with specific inhibitors of Notch (DAPT), AKT (LY294002) or ERK (U0126)...Finally, GSK650394 treatment of human M(IL-4) increased the levels of PPARG mRNA and its protein, indicating a negative role of SGK1 in M(IL-4) function. Overall, we report that the Notch signaling and AKT pathways cooperatively regulate SGK1 expression in M(IL-4) where SGK1, in turn, plays an important role in suppressing IL-4-induced PPAR expression.
  • ||||||||||  LY294002 / Eli Lilly, PD98059 / Wayne State University
    Journal, IO biomarker:  Euphorbia angustifolia lactone B inhibits A549 proliferation and induces apoptosis. (Pubmed Central) -  Mar 16, 2022   
    Moreover, 20 μ mol/L LY294002 (an PI3K inhibitor) + 120μg/mL JB and 10μmol/L PD98059 (an ERK inhibitor) +120μg/mL JB also increased apoptosis rates of A549 cells. JB could induced cell apoptosis through promoting endogenous mitochondrial signal transduction pathway and inhibiting PI3K/ERK pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects. (Pubmed Central) -  Mar 15, 2022   
    Moreover, administration of the PI3K/AKT inhibitor LY294002 abolished amelioration by SOMCL-668 of chronic PCP-induced schizophrenia-related behaviors by inhibition of BDNF expression. The present data provide initial, proof-of-concept evidence that allosteric modulation of the sigma-1 receptor may be a novel approach for the treatment of psychotic illness.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Calcium-Prolactin Secretion Coupling in Rat Pituitary Lactotrophs Is Controlled by PI4-Kinase Alpha. (Pubmed Central) -  Mar 15, 2022   
    Wortmannin, a PI3K and PI4K inhibitor, but not LY294002, a PI3K inhibitor, blocked spontaneous action potential driven PRL release with a half-time of ~20 min when applied in 10 µM concentration, leading to accumulation of intracellular PRL content...In contrast, PIK93, a specific inhibitor of PI4KB, and ISA2011B and UNC3230, specific inhibitors of PIP5K1A and PIP5K1C, respectively, did not affect PRL release. These experiments revealed a key role of PI4KA in calcium-secretion coupling in pituitary lactotrophs downstream of voltage-gated and PI(4, 5)P2-dependent calcium signaling.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  Suppression of JNK/ERK dependent autophagy enhances Jaspine B derivative-induced gastric cancer cell death via attenuation of p62/Keap1/Nrf2 pathways. (Pubmed Central) -  Mar 11, 2022   
    Meanwhile, C-2 triggered autophagy in gastric cancer cells, inhibition of which with LY294002 can enhance the anti-proliferative activity of C-2...Finally, p62 binds Keap1 competitively to release Nrf2, boosting Nrf2 translocation from the cytoplasm to the nucleus and triggering expression of Nrf2 target genes, so enhancing survival. C-2 inhibited the growth of gastric cancer cells, while JNK/ERK dependent autophagy antagonized C-2 induced cell growth inhibition through p62/Keap1/Nrf2 pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT-IKK/STAT3 Axis. (Pubmed Central) -  Mar 11, 2022   
    In the in vitro experiments, the phosphatidylinositol three kinase (PI3K) inhibitor LY294002 could abrogate the anti-inflammation and antifibrosis therapeutic effects of Cal, demonstrating that the cardioprotective effects of Cal were mediated through upregulations of PI3K and serine/threonine kinase (AKT). Cal inhibited inflammation and fibrosis via activation of the PI3K-AKT pathway in H9C2 cells, fibroblasts, and heart failure in postacute myocardial infarction rats.
  • ||||||||||  LY294002 / Eli Lilly
    PTEN loss is associated with elevation of cell cycle signature in human glioblastoma transcriptome (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_7280;    
    Additionally, RCC2 silencing and a PI3K inhibitor LY294002 inhibit glioblastoma cell viability in a synergistic manner...RCC2 was shown to be a key regulator of cell cycle progression. To further explore the RCC1 and RCC2 roles, we will find the potential downstream target of RCC1 and RCC2 and its potential therapeutic effect in vivo.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  Panax notoginseng saponins induce apoptosis in retinoblastoma Y79 cells via the PI3K/AKT signalling pathway. (Pubmed Central) -  Mar 5, 2022   
    The effects of PNS and carboplatin on the proliferation of Y79 cells were examined using cell counting kit-8 assay...Cellular alterations following inhibition of the PI3K/AKT pathway using LY294002 were similar to those of PNS, the proliferation of Y79 cells was also inhibited, and cell apoptosis increased (P < 0.001)...Overall, we demonstrated that PNS effectively inhibited the proliferation and promoted the apoptosis of retinoblastoma Y79 cells. The apoptosis-promoting effect of PNS may involve the inhibition of the PI3K/AKT signalling pathway, which subsequently regulates the expression of apoptosis-related genes.
  • ||||||||||  LY294002 / Eli Lilly, Visudyne (verteporfin) / Novartis
    Journal:  PI3K/Akt/YAP signaling promotes migration and invasion of DLD-1 colorectal cancer cells. (Pubmed Central) -  Mar 5, 2022   
    Notably, the present study demonstrated that verteporfin mediated the suppression of migration and invasion of DLD-1 cells due to the decreased expression of YAP. Therefore, targeting YAP may be valuable for developing therapeutic strategies against CRC, and verteporfin may be an effective therapy to suppress the migration and invasion of CRC.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Assessment of tantalum nanoparticle-induced MC3T3-E1 proliferation and underlying mechanisms. (Pubmed Central) -  Mar 4, 2022   
    Taken together, these results indicate that Peoniflorin preconditioning protects the myocardial against I/R injury and inhibits myocardial apoptosis via the activation of the RISK pathway, highlighting the potential therapeutic effects of Peoniflorin on reducing myocardial I/R injury. Pretreatment with Triciribine or Rapamycin has a greater effect on pathway protein Akt, cell cycle arrest, autophagy protein, and cell proliferation but with inconsistent magnitude, which may be inferred that the Akt/mTOR pathway, as well as its feedback loop, were more likely involved in these processes.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Calycosin alleviates H O -induced astrocyte injury by restricting oxidative stress through the Akt/Nrf2/HO-1 signaling pathway. (Pubmed Central) -  Mar 3, 2022   
    Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H O -induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3-kinase inhibitor), indicating that calycosin-mediated regulation of oxidative-stress homeostasis involved Akt/Nrf2/HO-1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO-1 signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly, PD98059 / Wayne State University
    Preclinical, Journal:  Chemerin-9 stimulates migration in rat cardiac fibroblasts in vitro. (Pubmed Central) -  Mar 1, 2022   
    In summary, we for the first time revealed that chemerin-9 stimulates migration perhaps through the ROS-dependent activation of Akt and ERK via CMKLR1 in cardiac fibroblasts. It is proposed that chemerin plays a role in the pathogenesis of cardiac diseases.