LY294002 / Eli Lilly 
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  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage. (Pubmed Central) -  Dec 2, 2022   
    The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer's disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3β signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Procyanidin B2 alleviates oxidative stress-induced nucleus pulposus cells apoptosis through upregulating Nrf2 via PI3K-Akt pathway. (Pubmed Central) -  Dec 1, 2022   
    We then used siNrf2 and LY294002 to silence Nrf2 expression and block the PI3K/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited...Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Reversion of glucocorticoid-induced senescence and collagen synthesis decrease by LY294002 is mediated through p38 in skin. (Pubmed Central) -  Nov 29, 2022   
    Interestingly, the protective effect of LY was dose-dependently reversed by treatment with a p38 inhibitor and reached 2.9 ± 0.15 fold at dose 20 µM. Taken together, our results demonstrate that LY reduced CP-induced upregulation of the atrophy marker FKBP51, GR phosphorylation, and GR nuclear translocation via the activation of p38, whilst maintaining the anti-inflammatory effect of glucocorticoids.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  UCHL5 Promotes Proliferation and Migration of Bladder Cancer Cells by Activating c-Myc via AKT/mTOR Signaling. (Pubmed Central) -  Nov 27, 2022   
    Finally, bladder cancers with knockdown or overexpression of UCHL5 were treated with either SC79 or LY294002 to examine the participation of the AKT/mTOR signaling pathway and the expression of downstream targets c-Myc, SLC25A19, and ICAM5...All things considered, our findings show that increased UCHL5 expression stimulates AKT/mTOR signaling, subsequently triggering the expression of c-Myc, SLC25A19, and ICAM5, which in turn promotes carcinogenesis in bladder cancer. UCHL5 is therefore a potential target for therapy in bladder cancer patients.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  EphA4/ephrinA3 reverse signaling mediated downregulation of glutamate transporter GLAST in Müller cells in an experimental glaucoma model. (Pubmed Central) -  Nov 24, 2022   
    In Müller cells with ephrinA3 knockdown, the PI3K inhibitor LY294002 still decreased the protein levels of NF-κB p65 in the presence of EphA4-Fc, and the mRNA levels of GLAST were reduced by LY294002 and the NF-κB inhibitor SN50, respectively...Western blot and TUNEL staining showed that transfecting of Si-EFNA3 reduced Müller cell gliosis and RGC apoptosis in COH retinas. Our results suggest that activated EphA4/ephrinA3 reverse signaling induces GLAST downregulation in Müller cells via inhibiting PI3K/Akt/NF-κB pathways, thus contributing to RGC damage in glaucoma.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Bacterial polyphosphates induce CXCL4 and synergize with complement anaphylatoxin C5a in lung injury. (Pubmed Central) -  Nov 22, 2022   
    Pharmacologic blockade of PI3K (wortmannin, LY294002) antagonized polyphosphate-induced CXCL4 release from macrophages...C5a generation occurred in the lungs and bronchoalveolar lavage fluid (BALF) of polyphosphate-treated C57BL/6J mice. In conclusion, we demonstrate that polyphosphates govern immunomodulation in macrophages and promote acute lung injury.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Knockdown of CCR3 gene inhibits Proliferation, migration and degranulation of eosinophils in mice by downregulating the PI3K/Akt pathway. (Pubmed Central) -  Nov 22, 2022   
    Bone marrow cells from wild-type mice (WT) were harvested for primary culture and differentiated into mature EOS, which were then randomly divided into the control, 740Y-P, and LY294002 group...Mechanistically, CCR3 inhibited EOS's proliferation, migration, and degranulation by downregulating PI3K/Akt pathway. This data suggests that the knockout of the CCR3 gene in bone marrow cells may inhibit the function of EOS by downregulating the PI3K/Akt pathway, thereby affecting AR; thus, the CCR3 gene may be a target gene for AR therapy.
  • ||||||||||  LY294002 / Eli Lilly, foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma
    Journal:  Taurine attenuates neuronal ferroptosis by regulating GABA/AKT/GSK3β/β-catenin pathway after subarachnoid hemorrhage. (Pubmed Central) -  Nov 20, 2022   
    The protective effects of taurine on SLC7A11 and GPX4 expression were reversed by ICG001 treatment in vitro. Taken together, our findings revealed that taurine could improve neurological function and alleviate cerebral edema, oxidative stress and BBB disruption after SAH, which reduced neuronal ferroptosis by regulating the GABA/AKT/GSK3β/β-catenin signaling pathway.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. (Pubmed Central) -  Nov 18, 2022   
    The efficacy of combined treatment with natural product‑derived and chemotherapy agents including curcumin combined with 5‑fluorouracil, resveratrol combined with cisplatin and epigallocatechin‑3‑gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged...Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway‑associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas Akt activator SC79 exerted an opposite effect in CTGF expression...In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.
  • ||||||||||  Erbitux (cetuximab) / Eli Lilly, EMD Serono
    Journal:  Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway. (Pubmed Central) -  Nov 18, 2022   
    Our results confirmed that platycodin-D increased the cytotoxic effects of cetuximab, including inhibition of growth, migration, and invasion, via downregulation of PI3K and Akt phosphorylation in HCT116 and LoVo cells both in vitro and in vivo. Given these data, platycodin-D may sensitize KRAS-mutant colorectal cancer cells to cetuximab via inhibition of the PI3K/Akt signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  The prognostic value and mechanisms of centromere protein M in patients with lung adenocarcinoma. (Pubmed Central) -  Nov 18, 2022   
    In vitro studies, LUAD cell lines were treated with CENPM-short hairpin RNA (shRNA) (shCENPM), or transfected with CENPM overexpression plasmids with or without LY294002 (PI3K inhibitor) treatment...CENPM was upregulated in LUAD patients, and it correlated with higher pathological stages and poor survival rates. CENPM could affect cell proliferation, cell cycle, cell migration and invasion capacity, and apoptosis in LUAD cell lines via regulation of AKT1/mTOR signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  MiR-140-3p directly targets Tyro3 to regulate OGD/R-induced neuronal injury through the PI3K/Akt pathway. (Pubmed Central) -  Nov 15, 2022   
     These results confirm that ERS plays an important role in CIRI and that leptin can inhibit the activation of ERS through the PI3K/Akt pathway, thereby alleviating CIRI. These findings provide novel therapeutic targets for IS. MiR-140-3p directly targets Tyro3 to regulate cell viability and apoptosis of OGD/R-exposed N2a cells through the PI3K/Akt pathway, suggesting that miR-140-3p is a novel biomarker and therapeutic target for ischaemic stroke.
  • ||||||||||  LY294002 / Eli Lilly, PF-573228 / Pfizer
    Journal:  Periodontal Ligaments Enhance Neurite Outgrowth in Trigeminal Ganglion Neurons through Wnt5a Production Induced by Mechanical Stimulation. (Pubmed Central) -  Nov 15, 2022   
    Similarly, PF573228, a focal adhesion kinase inhibitor, attenuated Akt- and ERK1/2-phosphorylation and Wnt5a expression...These findings reveal the indirect mechanisms that Wnt5a, released from the connective tissues in response to mechanical stimulation, enhances the outgrowth of the peripheral nerves. Our study suggests that the peripheral connective tissues regulate peripheral nerve homeostasis and that Wnt5a signaling could be targeted for the treatment of peripheral nerve disorders.
  • ||||||||||  LY294002 / Eli Lilly, SB202190 / Amgen, PD98059 / Wayne State University
    Journal:  Seeking an Important Role on Metabolomics-Effects of β-Estradiol on Lipoprotein Metabolism in Mammary Tumors (Pubmed Central) -  Nov 12, 2022   
    In addition, the effect of E on active LPL secretion was markedly suppressed by an inhibitor of mammalian target of rapamycin complex (mTORC) 1 and 2, KU0063794, but not by the mTORC1 inhibitor, rapamycin. Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed the secretion of LPL by E. Stimulatory secretion of LPL by E from the tumor cells is closely associated with activation of mTORC2 rather than mTORC1, possibly via the MAPK cascade.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Long-term low-dose microcystin-LR exposure induces renal injury in mice by activating PI3K/AKT signaling pathway (Pubmed Central) -  Nov 12, 2022   
    Furthermore, a small interfering RNA (siRNA)-mediated decrease in the expression of rapamycin-insensitive companion of mTOR (Rictor), a pivotal component of mTORC2, suppressed the secretion of LPL by E. Stimulatory secretion of LPL by E from the tumor cells is closely associated with activation of mTORC2 rather than mTORC1, possibly via the MAPK cascade. MC- LR can activate inflammatory response and induce renal structural and functional damages in mice by activating the PI3K/AKT signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Gracillin exerts anti-melanoma effects in vitro and in vivo: role of DNA damage, apoptosis and autophagy. (Pubmed Central) -  Nov 6, 2022   
    Induction of DNA damage, inhibition of PI3K/AKT/mTOR signaling and suppression of STAT3 signaling are involved in gracillin-mediated cell cycle arrest, autophagic cell death and apoptosis, respectively, in melanoma cells. These findings provide novel insights into the anti-melanoma molecular mechanisms of gracillin, and suggest a potential role of gracillin in melanoma management.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  NGF regulates sertoli cell growth and prevents LPS-induced junction protein damage via PI3K/AKT/NFκB signaling. (Pubmed Central) -  Nov 5, 2022   
    We further demonstrated that NGF prevented the inflammatory response of Sertoli cells via the PI3K/AKT/NFκB signaling pathway, similar to the effect of the PI3K-inhibitor, LY294002, which is modified by the PI3K activator, 740Y-P. These results provide insights for devising strategies for protecting the male reproductive system and curing or preventing associated pathological conditions.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Maternal exposure to PM2.5 decreases ovarian reserve in neonatal offspring mice through activating PI3K/AKT/FoxO3a pathway and ROS-dependent NF-κB pathway. (Pubmed Central) -  Nov 2, 2022   
    While LY294002, a specific inhibitor of PI3K, reversed the overactivation of primordial follicles induced by PM2.5...While N-acetylcysteine (NAC) pretreatment abolished the increases of apoptosis, reactive oxygen species (ROS), p-p65 and p-IκBα levels in ovarian granulosa COV434 cells induced by PM2.5 exposure...Our data suggest that this involves the activation of the PI3K/AKT/FoxO3a pathway and the ROS-dependent NF-κB pathway. Our study implicates a link between maternal PM2.5 exposure and ovarian reserve in offspring, and improves our understanding of the effects of PM2.5 on reproductive health.