LY294002 / Eli Lilly 
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  • ||||||||||  BIBR1532 / Boehringer Ingelheim, LY294002 / Eli Lilly
    Journal:  PPARγ activation inhibits PDGF-induced pulmonary artery smooth muscle cell proliferation and migration by modulating TERT. (Pubmed Central) -  Jun 23, 2022   
    Inhibition of Akt with LY294002, knockdown of c-MYC by siRNA or suppression of telomerase activity with BIBR1532 repressed PDGF-induced PASMC proliferation and migration. Furthermore, activation of peroxisome proliferator-activated receptor γ (PPARγ) with pioglitazone suppressed PDGF-induced TERT expression and telomerase activation, leading to inhibition of PASMC proliferation and migration.
  • ||||||||||  LY294002 / Eli Lilly, dactolisib (RTB101) / Adicet Bio
    Journal:  Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma. (Pubmed Central) -  Jun 22, 2022   
    When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo. NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined with the autophagy inhibitor both in vitro and vivo, providing convincing experimental data for new molecular targeted therapy for LSCC.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Chloroquine Attenuates Asthma Development by Restoring Airway Smooth Muscle Cell Phenotype Via the ROS-AKT Pathway. (Pubmed Central) -  Jun 22, 2022   
    Using HO and PI3K inhibitor (LY294002), we found that the inhibition of oxidative stress level and ROS-AKT signal by chloroquine may serve as a potential mechanism that dedicates to the restoration of the phenotypic imbalance in ASM cells. Overall, the present findings suggested that chloroquine improves asthmatic airway function by controlling ASM cell phenotype shift, sketching a novel profile of chloroquine as a new therapeutic candidate for airway remodeling.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  A role for the calcium-sensing receptor in the expression of inflammatory mediators in LPS-treated human dental pulp cells. (Pubmed Central) -  Jun 15, 2022   
    Meanwhile, an opposite direction was found between the action of R568 and Calhex231, as well as the expression of the pro- (IL-1β, IL-6, COX2-derived PGE, and TNF-α) and anti-inflammatory (IL-10) mediators. The results provide the first evidence that CaSR-phosphatidylinositol-3 kinase (PI3K)-AKT-signaling pathway is involved in the release of inflammatory mediators in LPS-treated hDPCs, suggesting that the activation or blockade of CaSR may provide a novel therapeutic strategy for the treatment of pulp inflammatory diseases.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal, IO biomarker:  Medicarpin isolated from Radix Hedysari ameliorates brain injury in a murine model of cerebral ischemia. (Pubmed Central) -  Jun 11, 2022   
    In vitro studies revealed that medicarpin displayed strong anti-inflammatory activity by reducing nitric oxide (NO) production in lipopolysaccharide-stimulated microglial cells (BV2) with an IC around 5 ±1 (μM) and anti-apoptotic activity in neuronal cells (N2A) subjected to oxygen-glucose deprivation with an IC around 13 ± 2 (μM). Collectively, this is the first report to demonstrate that medicarpin, isolated from Radix Hedysari, ameliorates ischemic brain injury through its anti-inflammatory microglia/NO), anti-apoptotic (neuronal cells/OGD) and neuroprotective effects by activating the PI3K/Akt-dependent GSK-3 inactivation for upregulating β-catenin, which in turn decreases the expression/activation of p65NF-κB and caspase 3 and promotes the expression of neurogenic (DCX, BDNF, TrkB) and neuroprotective (Bcl2) factors in the brain.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Kaposi's sarcoma-associated herpes virus-derived microRNA K12-1 over-activates the PI3K/Akt pathway to facilitate cancer progression in HIV-related gastrointestinal Kaposi's sarcoma. (Pubmed Central) -  Jun 9, 2022   
    Collectively, this is the first report to demonstrate that medicarpin, isolated from Radix Hedysari, ameliorates ischemic brain injury through its anti-inflammatory microglia/NO), anti-apoptotic (neuronal cells/OGD) and neuroprotective effects by activating the PI3K/Akt-dependent GSK-3 inactivation for upregulating β-catenin, which in turn decreases the expression/activation of p65NF-κB and caspase 3 and promotes the expression of neurogenic (DCX, BDNF, TrkB) and neuroprotective (Bcl2) factors in the brain. In summary, we concluded that KSHV-derived miR-K12-1 activate the PI3K/Akt pathway to initiate and accelerate the development of KS, which convinces us that miR-K12-1 can be used as potential biomarkers for KS diagnosis, treatment and prognosis.
  • ||||||||||  MK-2206 / Merck (MSD), LY294002 / Eli Lilly
    Journal:  Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway. (Pubmed Central) -  Jun 8, 2022   
    These results demonstrate that AA protects ischemic cardiomyocytes by modulating glycophagy- and mitophagy-based energy metabolism through the PI3K/Akt and AMPK pathways. These findings demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent and was related to regulation of NO production in vascular endothelial cells through the PI3K/Akt/eNOS signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Formononetin Improves the Survival of Random Skin Flaps Through PI3K/Akt-Mediated Nrf2 Antioxidant Defense System. (Pubmed Central) -  Jun 8, 2022   
    Co-treatment with formononetin and LY294002 (15 mg/kg), a potent Phosphatidylinositol-3-kinase (PI3K) inhibitor, which aborted nuclear Nrf2 expression and phosphorylated Akt, indicating that formononetin-mediated Nrf2 activation was related to PI3K/Akt pathway...We highlighted the antioxidant effects of formononetin since the Nrf2 system was activated. Therefore, formononetin might be a promising candidate drug that can enhance survival of skin flaps.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Isoalantolactone Induces Cell Cycle Arrest, Apoptosis and Autophagy in Colorectal Cancer Cells. (Pubmed Central) -  Jun 4, 2022   
    Repression of autophagy with autophagy inhibitors chloroquine (CQ) and Bafilomycin A1 (Baf-A1) enhanced the anti-CRC effects of IATL, suggesting that IATL induces cytoprotective autophagy in CRC cells...Inhibition of AKT and mTOR activities using LY294002 and rapamycin, respectively, potentiated the inductive effects of IATL on autophagy and cell death...Collectively, our results demonstrated that in addition to inhibiting proliferation, inducing G0/G1-phase cell cycle arrest and apoptosis, IATL initiates cytoprotective autophagy in CRC cells by inhibiting the AKT/mTOR signaling pathway. These findings provide an experimental basis for the evaluation of IATL as a novel medication for CRC treatment.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Hydrogen Repairs LPS-Induced Endothelial Progenitor Cells Injury via PI3K/AKT/eNOS Pathway. (Pubmed Central) -  Jun 4, 2022   
    H also restored levels of phosphor-AKT (p-AKT), eNOS and phosphor-eNOS (p-eNOS) suppressed by LPS. LY294002 significantly inhibited the increase of p-AKT and eNOS and p-eNOS expression exposed by H. L-NAME significantly inhibited the increase of eNOS and p-eNOS expression induced by H. H repairs the dysfunctions of EPCs induced by LPS, which is mediated by PI3K/AKT/eNOS signaling pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Melatonin ameliorates nickel induced autophagy in mouse brain: diminution of oxidative stress. (Pubmed Central) -  May 31, 2022   
    The presence of inhibitors effectively demonstrates that, within the PI3K/AKT/mTOR pathway, autophagy occurs. In conclusion, these data suggest that Ni causes oxidative stress damage and induces autophagy within the mouse brain by inhibiting the PI3K/AKT/mTOR pathway, and that Mt can effectively alleviate the oxidative stress caused by Ni, and reducing Ni induces autophagy in the mouse brain through the PI3K/AKT/mTOR pathway.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Role of Chitinase-3-like Protein 1 in Cardioprotection and Angiogenesis by Post-Infarction Exercise Training. (Pubmed Central) -  May 30, 2022   
    Furthermore, HUVEC cells were treated in vitro with AMPK agonist-AICAR (a putative pharmacological memetic of exercise), recombinant human CHI3L1, PAR2 receptor blocker (AZ3451), and PI3K inhibitor (LY294002), respectively...AICAR increased HUVEC tubules formation and upregulated CHI3L1 and PAR2 and these changes were attenuated by PAR2 blocker. In conclusion, post-MI exercise training can effectively activate CHI3L1/PAR2 signaling, which led to the improved myocardial function and enhanced cardiac angiogenesis in the infarcted heart.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Synergistic effects of mechanical stimulation and crimped topography to stimulate natural collagen development for tendon engineering. (Pubmed Central) -  May 29, 2022   
    A wavy microgrooved surface (Y = 5.47sin(0.015x)) that biomimics tendon topography was observed to enhance the expression of collagen assembly molecules under mechanical loading, and the aforementioned pathways are particularly involved and verified with their respective inhibitors of LY-294002 and LMK-235...In this study, a mechanical stimulation deprivation model of rat tendon was established to reveal the mechanisms in tendon development and defined the key regulatory molecules including small leucine-rich proteoglycans, lysyl oxidase and collagen V. After ensuring the importance of biomimetic structure in tendon remodeling, crimped nanofibers were developed to verify these regulatory molecules, and demonstrated that mechanical stimulation significantly enhanced collagen assembly via PIK3 and HDAC4 pathways in biomaterial-regulated tendon regeneration. This study provides more insightful perspectives in the physiologically remodeling progression of tendon collagen and design of tendon scaffolds.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Transcription Factor E2F1 Exacerbates Papillary Thyroid Carcinoma Cell Growth and Invasion via Upregulation of LINC00152. (Pubmed Central) -  May 29, 2022   
    In addition, E2F1 induced LINC00152 overexpression, which accelerated cell proliferation, migration, and invasion by activating the PI3K/AKT axis, whereas the administration of LY294002, the inhibitor of PI3K, led to reversal of the same...Our findings highlighted that E2F1 augmented PTC cell proliferation and invasion by upregulating LINC00152 and the PI3K/AKT axis. Our discovery provides therapeutic implications for PTC alleviation.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  27-Hydroxycholesterol induces expression of zonula occludens-1 in monocytic cells via multiple kinases pathways. (Pubmed Central) -  May 26, 2022   
    Drugs that are reported to suppress DC differentiation also inhibited 27OHChol-mediated expression and the localization of ZO-1, indicating the coincidence of ZO-1 upregulation and DC differentiation. These results suggest that ZO-1 is differentially expressed while monocytes differentiate into DCs in the presence of 27OHChol via pathways in which distinct signaling molecules are involved.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  Asthma susceptibility in prenatal nicotine-exposed mice attributed to β-catenin increase during CD4 T cell development. (Pubmed Central) -  May 20, 2022   
    Moreover, inhibiting PI3K-AKT by LY294002 abrogated nicotine-mediated β-catenin level increase and thymopoiesis abnormalities, and an α7 nAChR antagonist (α-btx) also reversed nicotine-induced PI3K-AKT activation. Our findings provide strong evidence that PNE is a risk factor for T cell deviation and postnatal asthma, and revealed that nicotine-induced β-catenin level increase induces thymopoiesis abnormalities.
  • ||||||||||  LY294002 / Eli Lilly
    Biomarker, Journal:  TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer. (Pubmed Central) -  May 19, 2022   
    Our results provide new evidence for the brain toxicity of SMX and its residual danger in the environment and aquatic organisms. TEAD4 is closely correlated with poor prognosis in BLCA and mediates its metastasis through regulating EMT via PI3K/AKT pathway, proving that TEAD4 is not only an effective biomarker for predicting the prognosis but also a great potential target for treatment of metastatic BLCA.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Longevity Effects of DMSO-Solubilized Rapamycin and Other Compounds in y w Male Drosophila melanogaster. (Pubmed Central) -  May 14, 2022   
    Experiments are in progress to test the effects of high dose rapamycin in male and female flies of several strains, comparing ethanol and DMSO solvents, different food recipes, lighting and storage conditions. A current conclusion is that rapamycin is not universally beneficial in Drosophila and that inhibitors of various kinases at the doses studied have limited or no effect on longevity.