LY294002 / Eli Lilly 
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  • ||||||||||  LY294002 / Eli Lilly, PTC-209 / PTC Therap
    Journal:  The ErbB3 Receptor Restricts Bmi1 to Regulate Paneth Cells. (Pubmed Central) -  May 14, 2022   
    Furthermore, BMI1 activity promotes LYZ1 expression. Together, these results support our hypothesis that ErbB3 regulates secretory cell differentiation through BMI1 in the intestinal epithelium.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Effect of Zinc in Submandibular Salivary Gland Branching Morphogenesis. (Pubmed Central) -  May 14, 2022   
    Together, these results support our hypothesis that ErbB3 regulates secretory cell differentiation through BMI1 in the intestinal epithelium. Collectively, these data clearly illustrate that the Zn is essential element during salivary gland organogenesis through activation of the PI3Kinase-AKT pathway.
  • ||||||||||  Jakafi (ruxolitinib) / Novartis, Incyte, LY294002 / Eli Lilly
    INFLUENCE OF INFLAMMATION ON ANGIOGENIC FACTORS IN CHRONIC LYMPHOCYTIC LEUKEMIA () -  May 13, 2022 - Abstract #EHA2022EHA_1153;    
    Conclusion We demonstrated increased level of angiogenic factors in CLL, while pro-inflammatory IL-6 and angiogenic VEGF preferentially stimulated HIF1α. Further studies with clinical data of CLL patients will indicate their potential role in diagnosis, progression, and response to therapy.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Baccharin from Brazilian green propolis induces neurotrophic signaling pathways in PC12 cells: potential for axonal and synaptic regeneration. (Pubmed Central) -  May 10, 2022   
    We used pharmacological inhibitors (K252a, LY294002, and U0126), and ELISA (phospho-trkA, phospho-Akt, and phospho-MEK) to investigate the involvement of trkA receptor, PI3k/Akt pathway, and MAPK/Erk pathway, respectively...Additionally, in silico predictions of baccharin showed favorable physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness. Altogether, these findings suggest that baccharin is a promising neurotrophic agent whose therapeutic application in neurodegeneration should be further investigated.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  PDGFRβ Modulates Aerobic Glycolysis in Osteosarcoma HOS Cells via the PI3K/AKT/mTOR/c-Myc Pathway. (Pubmed Central) -  May 6, 2022   
    PI3K pathway inhibitor LY294002 or MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to carry out western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRβ mainly activated the PI3K/AKT/mTOR/ c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRβ provides a novel metabolic therapeutic target for osteosarcoma.
  • ||||||||||  LY294002 / Eli Lilly, thapsigargin / University of Nottingham, Pirbright Institute
    Journal:  PKC signaling involved in PTTH-stimulated prothoracic glands in the silkworm, Bombyx mori. (Pubmed Central) -  May 6, 2022   
    Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation...A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation...PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signaling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signaling is involved in ecdysteroid secretion in Bombyx PGs.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Regulation of mouse primordial follicle formation by signaling through the PI3K pathway. (Pubmed Central) -  May 6, 2022   
    The delay in cyst breakdown was mitigated when ovaries were dually dosed with LY294002 and KITL, suggesting that while KIT may signal through PI3K to promote cyst breakdown, other signaling networks downstream of the receptor could compensate. These observations unearth a role for PI3K signaling in the establishment of the ovarian reserve and suggest that PI3K might be the primary mediator of KIT-induced cyst breakdown and primordial follicle formation in the mouse ovary.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Ligustrazine protects against chronic hypertensive glaucoma in rats by inhibiting autophagy via the PI3K-Akt/mTOR pathway. (Pubmed Central) -  Apr 30, 2022   
    Additionally, ligustrazine significantly increased the protein levels of phosphorylated PI3K (p-PI3K), protein kinase B (p-Akt), and mTOR (p-mTOR) in glaucoma rats, whereas such increases were attenuated by rapamycin or Ly294002. These results demonstrate that ligustrazine is protective in experimental glaucoma by inhibiting autophagy via the activation of the PI3K-Akt/mTOR pathway, providing compelling evidence that ligustrazine is potentially therapeutic for patients with glaucoma.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Development of New Thiophene-Containing Triaryl Pyrazoline Derivatives as PI3Kγ Inhibitors. (Pubmed Central) -  Apr 30, 2022   
    The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74)...The molecular docking simulation indicated that the binding pattern of 3s into PI3Kγ was preferable than that of PI3Kα, with more hydrogen bond, more π-involved interactions, and fewer π-sulfur interactions. The information in this work is referable for the further development of selective inhibitors for specific isoforms of PI3K.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Semaphorin 7A accelerates the inflammatory osteolysis of periapical lesions. (Pubmed Central) -  Apr 27, 2022   
    SEMA7A likely aggravates the inflammatory reaction and bone destruction of existing periapical lesions. The proinflammatory role of SEMA7A in hPDLCs could partially be mediated through the AKT signaling transduction pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Insulin activates LC-PUFA biosynthesis of hepatocytes by regulating the PI3K/Akt/mTOR/Srebp1 pathway in teleost Siganus canaliculatus. (Pubmed Central) -  Apr 27, 2022   
    Moreover, SCHL cells treated with different PI3K/Akt pathway inhibitors (LY294002, Wortmannin, AKTi-1/2) alone or combined with insulin decreased the mRNA levels of PI3K/Akt/mTOR downstream signaling genes, including Δ6Δ5 fads2, Δ4 fads2, elovl5, elovl4 and srebp1...The results of fatty acid composition analysis of hepatocytes showed that insulin stimulation increased the Δ6Δ5 Fads2-dependent PUFA desaturation indexes, Elovl5-dependent PUFA elongation indexes had upward trends, and consequently LC-PUFA contents increased. Taken together, these results indicated that insulin activated LC-PUFA biosynthesis probably through PI3K/Akt/mTOR/Srebp1 pathway in S. canaliculatus hepatocytes.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Poly(I:C) attenuates myocardial ischemia/reperfusion injury by restoring autophagic function. (Pubmed Central) -  Apr 26, 2022   
    Mechanistically, poly(I:C) activated the PI3K/AKT/mTOR pathway to induce autophagy, which was abolished by LY294002 (PI3K antagonist), rapamycin (autophagy activator and mTOR inhibitor), or 3-methyladenine (autophagy inhibitor), suggesting either inhibition of the PI3K/Akt/mTOR pathway or autophagy activity interrupt the beneficial effect of poly(I:C) preconditioning. In conclusion, poly(I:C) promotes cardiomyocyte survival from ischemia/reperfusion injury by regulating autophagy via the PI3K/Akt/mTOR pathway.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  miR-205 Reverses MDR-1 Mediated Doxorubicin Resistance via PTEN in Human Liver Cancer HepG2 Cells. (Pubmed Central) -  Apr 23, 2022   
    Finally, we found that miR-205 was down-regulated in HepG2/DOX cells, and its overexpression led to enhancing apoptosis with re-sensitization of HepG2/DOX cell lines to DOX through PTEN/PI3K/ Akt/MDR1 pathway. These findings may introduce miR-205 as a predictive biomarker and a potential treatment target for liver cancer therapy during MDR.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Glucosamine enhances proliferation, barrier, and anti-oxidative functions in porcine trophectoderm cells. (Pubmed Central) -  Apr 22, 2022   
    The addition of 0.25 mmol L GlcN enhanced the phosphorylation of mTOR signaling proteins, which can be inhibited by the inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002...The addition of 0.5 mmol L GlcN increased the protein expression of zonula occludens-3 (ZO-3), claudin-3, and claudin-4 in pTr cells, while inhibited the downregulation protein of claudin-1 and claudin-3 brought about by oxidative stress. Collectively, GlcN plays an important role in promoting proliferation and stimulating the mTOR cell signaling pathway, as well as ameliorating oxidative stress and augmenting barrier functions in pTr cells.
  • ||||||||||  colistin sulphate / Generic mfg.
    Journal:  Colistin-induced pulmonary toxicity involves the activation of NOX4/TGF-β/mtROS pathway and the inhibition of Akt/mTOR pathway. (Pubmed Central) -  Apr 21, 2022   
    Whereas, activation of autophagy by rapamycin pretreatment of A549 cells partly abolished colistin-induced cytotoxicity, mitochondrial dysfunction, and apoptosis. This is first study to show that colistin-induced pulmonary toxicity involves the activation of TGF-β/NOX4/mtROS pathway and the inhibition of Akt/mTOR pathway in lung tissues of mice and highlights the key protective role of autophagy activation.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Protective effect of growth differentiation factor 15 in sepsis by regulating macrophage polarization and its mechanism. (Pubmed Central) -  Apr 21, 2022   
    The mouse macrophages were cultured and treated with lipopolysaccharide (LPS), and some cells were intervened with GDF15 and LY294002...GDF15 regulates macrophage polarization through activating the PI3K/Akt signaling pathway and has a protective effect on survival and the cardiac function of patients with sepsis and sepsis mouse models. The increase in serum GDF15 level is closely related to severity and mortality in patients with sepsis and is therefore a prognostic marker of sepsis.
  • ||||||||||  cisplatin / Generic mfg.
    Preclinical, Journal, IO biomarker:  Maltol mitigates cisplatin-evoked cardiotoxicity via inhibiting the PI3K/Akt signaling pathway in rodents in vivo and in vitro. (Pubmed Central) -  Apr 20, 2022   
    In mice, maltol apparently induced PI3K/Akt in heart tissues and protected against cisplatin-induced cardiotoxicity. In conclusion, maltol exerted the protective effects against cisplatin-induced cardiotoxicity, at least partially by inhibiting the activation of PI3K/Akt signaling pathways in cardiomyocytes, to ease oxidative stress, and alleviate reactive oxygen species-mediated apoptosis.