LY294002 / Eli Lilly 
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  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Preclinical, Journal:  Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats. (Pubmed Central) -  Jan 13, 2021   
    Ten healthy SD rats were selected as a control group, thirty-six successfully established model rats were randomly divided into the model group, mir-124-agomir, mir-124-antagomir, mir-124-agomir+ LY294002 group (combined group), with 9 rats in each group...The level of miR-124, PI3K, Akt was positively correlated with the latent time of seizures in rats, and the level of miR-124 was positively correlated with the level of PI3K, Akt (P< 0.05). In conclusion, miR-124 can play a protective role in temporal lobe epilepsy by promoting PI3K/Akt signaling pathway, including the protection of cognitive function, which may be a potential target for clinical treatment of intractable epilepsy in the future.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Neuroprotective effects of mGluR5 activation through the PI3K/Akt pathway and the molecular switch of AMPA receptors. (Pubmed Central) -  Jan 8, 2021   
    These protective effects of DHPG and VU0092273 were prevented by inhibition of PI3K/Akt pathway by LY294002...Furthermore, immunohistochemical assays confirmed the neuroprotective effect of VU0092273 and revealed activation of glia, indicating the involvement reactive astrogliosis in the mechanisms of neuroprotection. Our data suggest that selective activation/potentiation of mGlu5 signalling represents a promising strategy for the development of new interventions to reduce or prevent ischemia-induced neuronal death.
  • ||||||||||  bleomycin / Generic mfg.
    Journal:  CXCL16/CXCR6 axis promotes bleomycin-induced fibrotic process in MRC-5 cells via the PI3K/AKT/FOXO3a pathway. (Pubmed Central) -  Jan 8, 2021   
    Our data suggest that selective activation/potentiation of mGlu5 signalling represents a promising strategy for the development of new interventions to reduce or prevent ischemia-induced neuronal death. CXCL16/CXCR6 axis promotes proliferation and collagen production of MRC-5 cells by the PI3K/AKT/FOXO3a signaling pathway, and inhibition of the CXCL16/CXCR6 axis may provide a new therapeutic strategy targeting pulmonary fibrosis.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  HER4 promotes the growth and metastasis of osteosarcoma via the PI3K/AKT pathway. (Pubmed Central) -  Jan 7, 2021   
    Notably, PI3K/AKT inhibitor LY294002 significantly inhibited the effects of HER4 via the downregulation of pAKT, Ki67, and MMP9...The present study suggests that HER4 may promote the growth and metastasis of osteosarcoma via the PI3K/AKT pathway. The HER4/PI3K/AKT pathway could serve as a potential target for the treatment of osteosarcoma.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal, IO biomarker:  Paris saponin VII enhanced the sensitivity of HepG2/ADR cells to ADR via modulation of PI3K/AKT/MAPK signaling pathway. (Pubmed Central) -  Jan 6, 2021   
    Moreover, the combination of ADR (5 nM), PS VII (1.98 μM), and LY294002 (PI3K/AKT inhibitor, 20 μM)/SB203580 (P38 inhibitor, 20 μM) for 48 hours could further decreased the HepG2/ADR cell viability, but induced cell apoptosis, accompanying with the decreased expressions of drug-resistant genes. PS VII could downregulate the expressions of drug-resistance genes, increase intracellular accumulation of ADR, promote cell apoptosis, and enhance the sensitivity of HepG2/ADR cells to ADR via PI3K/AKT/MAPK.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Preclinical, Journal:  Exogenous IGF-1 improves cognitive function in rats with high-fat diet consumption. (Pubmed Central) -  Jan 6, 2021   
    Neuronal cells HT22 were treated with nothing, IGF-1, IGF-1 + LY294002 or IGF-1 + 666-15...Then, we blocked the pathway and found that these blockers attenuated the protective effects of PEG-IGF-1. In conclusion, IGF-1 improved cognitive function and anxiety behavior in high-fat diet rats and inhibited inflammation and oxidative stress in hippocampus tissue through activation of PI3K/Akt/CREB pathway.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
    Journal, IO biomarker:  Kaji-Ichigoside F1 and Rosamultin Protect Vascular Endothelial Cells against Hypoxia-Induced Apoptosis via the PI3K/AKT or ERK1/2 Signaling Pathway. (Pubmed Central) -  Jan 6, 2021   
    In conclusion, Kaji-ichigoside F1 protected vascular endothelial cells against hypoxia-induced apoptosis by activating the ERK1/2 signaling pathway, which positively regulated the NF-κB signaling pathway and negatively regulated the PI3K/AKT signaling pathway. Rosamultin protected vascular endothelial cells against hypoxia-induced apoptosis by activating the PI3K/AKT signaling pathway and positively regulating ERK1/2 and NF-κB signaling pathways.
  • ||||||||||  desloratadine / Kaken, Incepta, Merck (MSD), Generic mfg.
    Journal, IO biomarker:  Desloratadine, a Novel Antigrowth Reagent for Bladder Cancer. (Pubmed Central) -  Jan 6, 2021   
    The level of interleukin 6 was reduced in desloratadine-treated cells, while upregulation of interleukin 6 significantly abolished the anticancer activity of desloratadine in cell invasion and Bcl-2, Bax, Beclin1, LC3-I/II, N-cadherin, and E-cadherin expression in EJ cells. Taken together, our data suggest a potential anticancer activity of desloratadine on cell growth and invasion for bladder cancer, which may be mediated by diminishing the epithelial-to-mesenchymal transition and interleukin 6.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Sex Differences in the Pro-Angiogenic Response of Human Endothelial Cells: Focus on PFKFB3 and FAK Activation. (Pubmed Central) -  Jan 5, 2021   
    Finally, digitoxin treatment, which inhibits Y576/577 FAK phosphorylation, abolished sexual dimorphism in HUVEC migration. These findings unravel complementary modulation of HUVEC functional phenotypes and signaling molecules involved in angiogenesis by hormone microenvironment and sex-specific factors, and highlight the need for sex-oriented pharmacological targeting of endothelial function.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  HnRNP-F promotes the proliferation of bladder cancer cells mediated by PI3K/AKT/FOXO1. (Pubmed Central) -  Jan 5, 2021   
    HnRNP-F expression was significantly decreased by treatment with the PI3K/AKT signalling pathway inhibitor LY294002, whereas hnRNP-F knockdown did not significantly affect PI3K or AKT expression, suggesting that hnRNP-F is likely a downstream target of the PI3K/AKT pathway...To sum up, our findings suggest that hnRNP-F expression is regulated by the PI3K/AKT-mediated phosphorylation of FOXO1, with phosphorylation inhibiting FOXO1, which subsequently allows hnRNP-F to promote proliferation. This finding is a novel discovery in BC and could help reveal the mechanism of BC progression.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, ABT-737 / AbbVie
    [VIRTUAL] Combination therapies targeting apoptosis pathways in paediatric AML () -  Jan 5, 2021 - Abstract #BSHI2020BSH-I_298;    
    (ABT‐737‐ 100 nmol/l + Purvalanol A‐ 1 µmol/l) (ABT‐737‐ 100 nmol/l + LY294002‐ 2 µmol/l)...Our combinations showed interesting therapeutic potential, which to our knowledge has not been reported by other groups investigating these drug pairings. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.
  • ||||||||||  quercetin (LY294002) / Eli Lilly, Alverix (amiloride hydrochloride) / Remedica
    [VIRTUAL] ENDOSOMAL ESCAPE IS ESSENTIAL AND RATE-LIMITING IN THE SEEDED AGGREGATION OF TAU () -  Dec 24, 2020 - Abstract #ADPD2021ADPD_1211;    
    Our study identifies the penetration of endosomal membranes as a critical upstream step in the seeded aggregation of tau. The work demonstrates that contact between tau assemblies and native tau pools is rate-limiting and essential to seeded aggregation.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Erratum. (Pubmed Central) -  Dec 23, 2020   
    Our study demonstrated that TRAF4 was involved in promoting HCC cell migration and invasion. The process was induced by the EMT through activation of the PI3K/Akt signaling pathway.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal, IO Biomarker:  Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia (Pubmed Central) -  Dec 22, 2020   
    We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor)...In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Antiosteoclastic bone resorption activity of osteoprotegerin via enhanced AKT/mTOR/ULK1-mediated autophagic pathway. (Pubmed Central) -  Dec 18, 2020   
    Treatment with OPG and chloroquine, an autophagy inhibitor, attenuated OPG-induced inhibition of osteoclastic bone resorption, whereas rapamycin (RAP), an autophagy inducer, enhanced OPG-induced inhibition of differentiation, survival, and bone resorption activity of osteoclasts...LY294002, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT pathway inhibitor, attenuated the decline in pAKT, but enhanced the decline in pmTOR and the increase in pULK1 following OPG treatment...The PI3K inhibitor 3-methyladenine partly blocked OPG-induced autophagy. Thus, the results revealed that OPG inhibits osteoclast bone resorption by inducing autophagy via the AKT/mTOR/ULK1 signaling pathway.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Preclinical, Journal, IO Biomarker:  Effects of ranolazine on cardiac function in rats with heart failure. (Pubmed Central) -  Dec 18, 2020   
    Thus, the salvage of oxidative-stress-induced apoptotic cardiomyocytes in I/R by CST might involve activationβ2 receptor and regulation of PI3K/Akt signaling in reperfusion injury salvage kinase (RISK) pathway. Ranolazine improved cardiac function and inhibited myocardial apoptosis in rats with CHF, which could be attributed to the regulation of AKT phosphorylation.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways. (Pubmed Central) -  Dec 17, 2020   
    We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGFβ and PI3K pathways, respectively, and found that p53, p21 and p16 were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGFβ, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-β-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGFβ and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Melatonin ameliorates pressure overload-induced cardiac hypertrophy by attenuating Atg5-dependent autophagy and activating the Akt/mTOR pathway. (Pubmed Central) -  Dec 16, 2020   
    Male C57BL/6 mice that received adenovirus carrying cardiac-specific Atg5 (under the cTNT promoter; Ad-cTNT-Atg5) underwent transverse aortic constriction (TAC) or sham operation and received an intraperitoneal injection of melatonin (10 mg/kg/d), vehicle or LY294002 (10 mg/kg/d) for 8 weeks...As expected, Akt/mTOR pathway inhibition or cardiac-specific Atg5 overexpression restrained melatonin alleviation of pressure overload-induced cardiac hypertrophy. These results demonstrated that melatonin ameliorated pressure overload-induced cardiac hypertrophy by attenuating Atg5-dependent autophagy and activating the Akt/mTOR pathway.
  • ||||||||||  tyrphostin (AG 490) / EMD Serono, Yissum Research Development Company, quercetin (LY294002) / Eli Lilly
    Preclinical, Journal:  Intracellular interplay between cholecystokinin and leptin signalling for satiety control in rats. (Pubmed Central) -  Dec 16, 2020   
    Taken together, these results suggest that leptin and CCK receptors may both contribute to short-term satiety, and leptin could positively modulate CCK signalling. Notably, nuclear pSTAT3 levels in this experimental paradigm were negatively correlated with satiety levels, contrary to the generally described transcriptional regulation for long-term satiety via leptin receptors.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Effects of NOX4 on radiosensitivity of nasopharyngeal carcinoma cells by activating the PI3K/AKT pathway (Pubmed Central) -  Dec 16, 2020   
    Compared with the NOX4+radiation group, the proliferation ability of nasopharyngeal carcinoma cells in the NOX4+radiation+LY294002 group was reduced (72 h absorbance (A) value: 0.79 vs. 0.56), while the apoptotic rate was increased (3.8% vs. 8.1%). NOX4 can inhibit radiosensitivity of nasopharyngeal carcinoma cells possibly by activating PI3K/AKT pathway.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  HDL (High-Density Lipoprotein) and ApoA-1 Potentially Modulate Pancreatic α-Cell Glucagon Secretion. (Pubmed Central) -  Dec 15, 2020   
    These results support the notion that HDL and ApoA-1 modulate glucagon expression and secretion by binding their cognate receptor SCARB-1, and activating the PI3K/Akt/FoxO1 signaling cascade in an in vitro α-cell model. Overall, these results raise the hypothesis that HDL and ApoA-1 may have a role in modulating glucagon secretion.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal, IO Biomarker:  Oncogenic Role of NUPR1 in Ovarian Cancer. (Pubmed Central) -  Dec 12, 2020   
    In addition, NUPR1 knockdown could effectively inhibit tumor growth of mice in vivo. In summary, NUPR1 has a carcinogenic effect in ovarian cancer, and the oncogenic effect of NUPR1 in ovarian cancer may be achieved by the AKT pathway.