LY294002 / Eli Lilly 
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  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Hyperphosphorylation of HDAC2 promotes drug resistance in a novel dual drug resistant mouse melanoma cell line model: an in vitro study. (Pubmed Central) -  Jan 13, 2022   
    The dual drug-resistant mouse melanoma, B16F10R, was established by treating the cells with a combination of U0126 (MEK1/2 inhibitor) and LY294002 (PI3K-AKT kinase inhibitor) in a dose-escalating manner till they attained a resistance fold factor of ≥2...The present study highlights the role of HDAC2, a cell cycle regulator, in the development of resistance to dual drugs in murine melanoma. Therefore, designing leads for targeting HDAC2 along with key signaling pathways may be explored in treatment strategies.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  DP from Euphorbia fischeriana S. mediated apoptosis in leukemia cells via the PI3k/Akt signaling pathways. (Pubmed Central) -  Jan 12, 2022   
    Therefore, designing leads for targeting HDAC2 along with key signaling pathways may be explored in treatment strategies. The in vivo and in vitro experimental results indicated that DP might inhibit the proliferation and induce the apoptosis of leukemia cells, which might be a result of suppressing the PI3k/Akt signaling pathways.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  The mechanism analysis using PI3K/AKT pathway for the effects of levocarnitine in the treatment of spermatogenic dysfunction. (Pubmed Central) -  Jan 12, 2022   
    LEV and LY294002 (a PI3K pathway inhibitor) were then administered...Besides, the morphology of testicular tissue in the GTW + LEV and LY + LEV groups was superior to that in the GTW group. We can to the conclusion that LEV may operate via the PI3K/AKT signalling pathway, with increases in PI3K, p-AKT, and BCL-2 protein and mRNA expression, so that the percentages of GC-1 spg cells apoptosis decrease, and the sperm count and motility improve.
  • ||||||||||  Fycompa (perampanel) / Eisai
    Journal:  The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neurons. (Pubmed Central) -  Jan 11, 2022   
    We can to the conclusion that LEV may operate via the PI3K/AKT signalling pathway, with increases in PI3K, p-AKT, and BCL-2 protein and mRNA expression, so that the percentages of GC-1 spg cells apoptosis decrease, and the sperm count and motility improve. Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic β-cells via the PI3K/Akt/FoxO1 signaling pathway. (Pubmed Central) -  Jan 11, 2022   
    Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002...The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic β-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Akt and its phosphorylation in nucleus accumbens mediate heroin-seeking behavior induced by cues in rats. (Pubmed Central) -  Jan 5, 2022   
    Akt is initially identified as one of the downstream targets of phosphatidylinositol-3 kinase (PI3K) and is involved in morphine reward and tolerance...Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS-induced heroin-seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p-Akt in the NAc...CS-induced heroin-seeking behavior was inhibited by downregulation of Akt1, but not β-arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin-seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  The oncogenic role of the cerebral endothelial cell adhesion molecule (CERCAM) in bladder cancer cells in vitro and in vivo. (Pubmed Central) -  Jan 4, 2022   
    The PI3K inhibitor LY294002 treatment manifested similar effects as CERCAM silencing on bladder cancer cell behaviors and partially impaired the promotive functions of CERCAM overexpression upon the capacity of bladder cancer cells to proliferate and invade...In vitro, CERCAM overexpression significantly promoted bladder cancer cell viability, DNA synthesis, and cell invasion and alters the cleaved-caspase3, E-cadherin, and N-cadherin expression pattern; in vivo, CERCAM silencing suppressed tumor growth in nude mice. The PI3K/AKT signaling is suspected of interfering participate in the functions of CERCAM in bladder carcinoma.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Acacetin Protects Myocardial Cells against Hypoxia-Reoxygenation Injury through Activation of Autophagy. (Pubmed Central) -  Jan 4, 2022   
    Moreover, we found that application of acacetin increased activation of the PI3K/Akt signaling pathway, whereas cotreatment with the PI3K inhibitor LY294002 reversed the inhibition of apoptosis and autophagy induced by acacetin. In conclusion, acacetin mitigated H/R injury by promoting autophagy through activating the PI3K/Akt/mTOR signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species. (Pubmed Central) -  Jan 4, 2022   
    In addition, scavenging of ROS by NAC resulted in a decreased expression of phospho-Akt, HK2 and Cyclin D1, and attenuates the ability of anchorage-independent growth ofL-02-As cells, suggested that ROS mediated the Akt activation in L-02-As cells. In summary, our results demonstrated that ROS contributes to the malignant phenotype of arsenic-transformed human hepatocyte L-02-As via the activation of Akt pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  AGEs promote calcification of HASMCs by mediating Pi3k/AKT-GSK3β signaling. (Pubmed Central) -  Jan 1, 2022   
    Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-β inhibitor) group...In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-β activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-β signaling.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Protease-activated receptor 4 causes Akt phosphorylation independently of PI3 kinase pathways. (Pubmed Central) -  Dec 30, 2021   
    We propose that 3.12 µM LY294002 is sufficient to inhibit PI3 kinase isoforms in platelets and higher concentrations might inhibit other pathways regulating Akt phosphorylation by AYPGKF. We conclude that Protease-activated receptor 4 (PAR4) might cause Akt phosphorylation through pathways distinctly different from those of Protease-activated receptor 1 (PAR1).
  • ||||||||||  sirolimus / Generic mfg.
    Preclinical, Journal:  Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats. (Pubmed Central) -  Dec 29, 2021   
    Consistently, the activation and inhibition of autophagy using rapamycin and LY294002 confirmed the regulatory effects of 11R‑VIVIT on autophagy. On the whole, the findings of the present study demonstrate that 11R‑VIVIT promotes fracture healing in osteoporotic rats and enhances the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3β-β-Catenin Signaling Axis. (Pubmed Central) -  Dec 25, 2021   
    Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide-3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Baicalein inhibits invasion and promotes apoptosis in glioma cells through the PI3K/Akt pathway. (Pubmed Central) -  Dec 23, 2021   
    These results suggest that Akt and AMPK are involved in the regulation of trophoblast mTOR activity in the placentas of pregnancies complicated by FGR and GDM with LGA infants. Baicalein treatment is able to suppress invasiveness and induce apoptosis of glioma cells through inactivating the PI3K/Akt pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Resistance training increases insulin-induced vasodilation in the mesenteric artery of healthy rats. (Pubmed Central) -  Dec 23, 2021   
    Forty-eight hours after the last session of the RT, the animals were sacrificed and vascular reactivity to insulin in the absence and presence of LY294002 (phosphatidylinositol 3-kinase inhibitors (PI3K), L-NAME (nitric oxide synthase (NOS) inhibitors) and BQ123 (endothelin A antagonist (ET-A) receptor)...When the Phe response was evaluated, there was a reduction in tension in the RT group compared to the CON group. The results suggest that RT improves vascular reactivity.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Mild hypothermia protects rat cortical neurons against oxygen-glucose deprivation/reoxygenation injury via the PI3K/Akt pathway. (Pubmed Central) -  Dec 22, 2021   
    When the PI3K inhibitor LY294002 was added, neuronal viability and the expression of pAkt and GLT-1 decreased, and extracellular glutamate concentration increased...There was no significant change in neuronal viability or the expression of pAkt and GLT-1 in the group treated with dihydrokainate, an inhibitor of GLT-1-function, compared with the mild hypothermia + OGD/R (HOGD) group, but extracellular glutamate concentration was increased. Consequently, mild hypothermia promoted glutamate clearance by regulating GLT-1 expression via the PI3K/Akt pathway, providing a neuroprotective effect against OGD/R injury.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Cholesterol Regulates Exosome Release in Cultured Astrocytes. (Pubmed Central) -  Dec 22, 2021   
    The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Oleate ameliorates palmitate-induced impairment of differentiative capacity in C2C12 myoblast cells. (Pubmed Central) -  Dec 16, 2021   
    The positive effect of OA on myoblast differentiative capacity disappeared if PI3K inhibitor LY294002 was added. In conclusion, our study showed that PA could destroy differentiative capacity of C2C12 myoblasts by affecting the expression of Pax7, MyoD and MyoG, and OA could improve this impairment through PI3K /Akt signaling pathway.
  • ||||||||||  loperamide / Generic mfg.
    Preclinical, Journal:  7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats. (Pubmed Central) -  Dec 16, 2021   
    The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP. Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.