- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Phloretin Suppresses Bone Morphogenetic Protein-2-Induced Osteoblastogenesis and Mineralization via Inhibition of Phosphatidylinositol 3-kinases/Akt Pathway. (Pubmed Central) - Nov 14, 2019
In addition, treatment with a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, LY294002, suppressed the mineralization and the expression of osteoblast differentiation markers other than ALP...The effects of GLUT1 silencing on osteoblast differentiation markers and mineralization were inconsistent with those of phloretin. Taken together, these findings suggest that phloretin suppressed osteoblastogenesis of ST2 and MC3T3-E1 cells by inhibiting the PI3K/Akt pathway, suggesting that the effects of phloretin may not be associated with glucose uptake inhibition.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), quercetin (LY294002) / Eli Lilly, tirabrutinib (GS-4059) / Ono Pharma, Gilead
Biomarker, Journal: Identification of Potential Biomarkers in Association With Progression and Prognosis in Epithelial Ovarian Cancer by Integrated Bioinformatics Analysis. (Pubmed Central) - Nov 14, 2019
The expression profiles GSE27651, GSE38666, GSE40595, and GSE66957 including 188 tumor and 52 nontumor samples were downloaded from the Gene Expression Omnibus database...We next identified four bioactive compounds (vorinostat, LY-294002,trichostatin A, and tanespimycin) based on ConnectivityMap...Furthermore, the univariate and multivariate Cox proportional hazards regression showed that ZWINT was independent prognostic indictor among EOC patients. The genes and pathways discovered in the above studies may open a new direction for EOC treatment.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Protective Effects of Ursolic Acid Against Cytotoxicity Induced by Corticosterone: Role of Protein Kinases. (Pubmed Central) - Nov 13, 2019
Inhibition of protein kinase A (PKA), protein kinase C (PKC) and, Ca/calmodulin-dependent protein kinase II (CaMKII), but not phosphoinositide 3-kinase(PI3K), by using the pharmacological the inhibitors: H-89, chelerythrine, KN-62, and LY294002, respectively totally abolished the cytoprotective effects of UA...These results indicate that the protective effect of UA against the cytotoxicity induced by corticosterone in HT22 cells may involve PKA, PKC, CaMKII, and ERK1/2 activation. The cytoprotective potential of UA against corticosterone-induced cytotoxicity and its ability to modulate intracellular signaling pathways involved in cell proliferation and survival suggest that UA may be a relevant strategy to manage stress-related disorders such as MDD.
- |||||||||| quercetin (LY294002) / Eli Lilly
Clinical, Journal: Maternal diabetes up-regulates NOX2 and enhances myocardial ischaemia/reperfusion injury in adult offspring. (Pubmed Central) - Nov 11, 2019
In cultured cardiomyocytes, high glucose increased mTOR phosphorylation, which was inhibited by the PI3 kinase inhibitor LY294002...In conclusion, maternal diabetes promotes VEGF-Akt-mTOR-NOX2 signalling and enhances myocardial I/R injury in the adult offspring. Increased ROS production from NOX2 is a possible molecular mechanism responsible for developmental origins of cardiovascular disease in offspring of diabetic mothers.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal, IO Biomarker: Granulocyte colony-stimulating factor improves neurological function and angiogenesis in intracerebral hemorrhage rats. (Pubmed Central) - Nov 11, 2019
Increased ROS production from NOX2 is a possible molecular mechanism responsible for developmental origins of cardiovascular disease in offspring of diabetic mothers. G-CSF enhanced PI3K/AKT signaling pathway activity, promoted Bcl-2 and VEGF expression, reduced nerve cell apoptosis, and enhanced tube capacity of VECs, which may be the mechanism of G-CSF in improving neurological function and angiogenesis after ICH.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: 14-3-3ζ binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells. (Pubmed Central) - Nov 8, 2019
This 14-3-3ζ-HBx interaction was partly impaired when Akt signaling transduction was blocked by LY294002...Additionally, 14-3-3ζ positively correlated with HBx to be overexpressed in the primary HCC tissues (r = 0.344) and metastatic PVTT (r = 0.348). In summary, findings of this study reveal a novel 14-3-3ζ-HBx interaction in HCC cells and suggest 14-3-3ζ as a candidate target for treating HBV-related HCC.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Effects of COL8A1 on the proliferation of muscle-derived satellite cells. (Pubmed Central) - Nov 6, 2019
The expression of P-Akt was unchanged after addition of LY294002 (a protein kinase inhibitor capable of blocking the signal transduction pathway of the phosphoinositide 3-kinase)...The dual-luciferase reporter assay revealed that EGR1 regulates the promoter activity of COL8A1. To our knowledge, this is the first study demonstrating that EGR1 positively regulates the expression of COL8A1, which in turn promotes the proliferation of bovine MDSCs via the PI3K/AKT signaling pathway.
- |||||||||| MK-2206 / Merck (MSD), Zyclara (imiquimod) / Mochida, Mylan, Bausch Health, quercetin (LY294002) / Eli Lilly
Journal: Cornulin Is Induced in Psoriasis Lesions and Promotes Keratinocyte Proliferation via PI3K-Akt Pathways. (Pubmed Central) - Nov 2, 2019
Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Bi S -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal Therapy of LoVo Cells In Vitro and In Vivo. (Pubmed Central) - Oct 31, 2019
Moreover, the mechanism studies also demonstrate that Bi S -Tween 20@LY294002 potently kills LoVo cancer cells under low-power near-infrared light irradiation, by downregulating the expression of heat shock protein 70 (HSP70) so as to increase the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated mitochondrial apoptosis pathway. The results demonstrate that the newly synthesized multifunctional nanoplatform paves a new avenue for accurate therapy of photothermal-resistant cancer.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Ghrelin-Induced Sodium Reabsorption Is Mediated by PKA and Microtubule-Dependent αEC Translocation in Female Rats. (Pubmed Central) - Oct 31, 2019
Seventy-two hours following uninephrectomy, 12-week-old female Sprague-Dawley rats received the following renal interstitial (RI) infusions for 1 hour after a 1-hour control: vehicle (n = 10), ghrelin (3 μg/minute; n = 8), ghrelin + phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 (0.1 μg/kg/minute; n = 7), ghrelin + protein kinase A (PKA) inhibitor adenosine 3'5'-cyclic monophosphorothioate, Rp-isomer (10 μg/kg/minute; n = 8), ghrelin + microtubule polymerization inhibitor nocodazole (0.3 μg/kg/minute; n = 7), or ghrelin + actin polymerization inhibitor cytochalasin D (0.3 μg/kg/minute; n = 6)...Neural precursor cell expressed, developmentally down-regulated 4 isoform 2 (Nedd4-2) dependent internalization of αEC was not affected by ghrelin, indicating that microtubule-dependent forward trafficking of αEC is necessary for anti-natriuretic responses to ghrelin. Taken together, these studies highlight the importance of PKA and microtubule polymerization in ghrelin-induced αEC-mediated Na reabsorption.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice. (Pubmed Central) - Oct 31, 2019
PI3K-Akt pathway and H3K27me3 form a feedback loop in rd1 retina, thus PI3K inhibitor LY294002 reduces phosphorylation of Ezh2 at serine 21 and enhances H3K27me3 deposition, and inhibiting H3K27me3 by DZNep can activate PI3K-Akt pathway by de-repressing gene expression of PI3K subunits Pik3r1 and Pik3r3. These findings suggest that histone methylation, especially H3K27me3 deposition is a novel mechanism and therapeutic target for retinal degenerative diseases, similar to H3K27me3-mediated ataxia-telangiectasia in Atmmouse.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Perfluorooctane sulfonate mediates secretion of IL-1β through PI3K/AKT NF-кB pathway in astrocytes. (Pubmed Central) - Oct 29, 2019
In addition, pretreatment with AKT inhibitor LY294002 could obviously attenuate PFOS-induced NF-κB activation and IL-1β secretion. Taken together, these results indicated that PFOS could facilitate reactive astrocytosis and the secretion of pro-inflammatory cytokines through AKT-dependent NF-κB signaling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Krüppel-like factor 8 regulates VEGFA expression and angiogenesis in hepatocellular carcinoma. (Pubmed Central) - Oct 24, 2019
KLF8-overexpressing HCC cells had a higher potential for inducing angiogenesis. Thus, our results indicate that KLF8 may induce angiogenesis in HCC by binding to the CACCC region of the VEGFA promoter to induce VEGFA promoter activity and through FAK to activate PI3K/AKT signaling to regulate HIF-1α expression levels.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: SERPIND1 Affects the Malignant Biological Behavior of Epithelial Ovarian Cancer via the PI3K/AKT Pathway: A Mechanistic Study. (Pubmed Central) - Oct 23, 2019
The addition of the PI3K/AKT pathway inhibitor LY294002 to SERPIND1-overexpressing cells could reverse the promoting effect of SERPIND1 on the malignant biological behavior of ovarian cancer cells...In conclusion, our results indicated that SERPIND1 could be an effective marker for assessing the prognosis of ovarian cancer. By elucidating its mechanism underlying the promotion of malignant biological behavior of ovarian cancer by SERPIND1, we demonstrated that SERPIND1 could potentially serve as a novel drug target.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Hepatitis B spliced protein (HBSP) suppresses Fas-mediated hepatocyte apoptosis via activation of PI3K/Akt signaling. (Pubmed Central) - Oct 20, 2019
Confirmedly, inhibition of PI3K by LY294002 reversed the effect of HBSP on Fas aggregation, FLIP expression, and cellular apoptosis...In particular, HBV variants associated with hepatoma carcinoma may down-regulate apoptosis of hepatocytes through enhanced HBSP expression. Our study also found that AKT is centrally involved in Fas-induced hepatocyte apoptosis and revealed interventions directed at inhibiting the activation or functional activity of AKT may be of therapeutic value in this process.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Upregulation of GLT-1 via PI3K/Akt Pathway Contributes to Neuroprotection Induced by Dexmedetomidine. (Pubmed Central) - Oct 17, 2019
Furthermore, using Atipamezole and LY294002, we found that dexmedetomidine significantly increased GLT-1 levels in astrocytes via activating α2 adrenergic receptor and PI3K/AKT pathway both in vitro and in vivo study. Overall, our present study indicated that dexmedetomidine had neuroprotective effects on ischemia stroke and upregulation of GLT-1 levels by PI3K/AKT dependent pathway might be the potential mechanism.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: PI4KIII inhibitor enviroxime impedes the replication of the hepatitis C virus by inhibiting PI3 kinases. (Pubmed Central) - Oct 16, 2019
Interestingly, the broad-spectrum phosphoinositide 3-kinase (PI3K) inhibitor LY294002 proved to be 10-fold less effective against the resistant replicons...Instead, we demonstrated that both molecules impede HCV replication at least partially by an inhibitory effect on PI3Ks. Moreover, HCV is able to bypass PI3K inhibition by acquiring mutations in its genome.
- |||||||||| doxorubicin hydrochloride / generics, irinotecan / generics
Preclinical, Journal: Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells. (Pubmed Central) - Oct 16, 2019
The mRNA level of occludin (OCLN), a tight junctional protein, was increased in the cisplatin (CDDP), doxorubicin (DXR), 7-ethyl-10-hydroxy-camptothecin, or gemcitabine-resistant human lung adenocarcinoma A549 cells...The level of p-Akt in A549/CDDP cells was higher than that in A549 cells, and the mRNA and protein levels of OCLN were suppressed by a phosphoinositide 3-kinase (PI3K)/Akt pathway inhibitor, LY-294002, suggesting that a PI3K/Akt pathway is involved in the elevation of OCLN expression...The accumulation inside the spheroids and toxicity of DXR were correlated with OCLN expression. Our data suggest that OCLN is not directly involved in the chemoresistance, but it enhances chemoresistance mediated by suppression of accumulation of anticancer drugs inside the spheroids.
- |||||||||| quercetin (LY294002) / Eli Lilly
Anti-Apoptotic Role of Phosphatidylinositol-3 Kinase (PI3-Kinase) in Angiotensin II-Induced Podocyte Injury (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3050;
PI3-kinase inhibitors, 3-MA and LY294002, and Atg5 siRNA further increased Ang II-induced podocyte apoptosis...Conclusion Our findings suggest that Ang II induces podocyte apoptosis, which could be prevented by PI3-kinase activation through the inhibition of SHIP2 and promoting autophagy. Funding Government Support - Non-U.S.
- |||||||||| tyrphostin (AG 490) / EMD Serono, Yissum Research Development Company, quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal, IO Biomarker: Adropin reduces hypoxia/reoxygenation-induced myocardial injury via the reperfusion injury salvage kinase pathway. (Pubmed Central) - Oct 12, 2019
Furthermore, no significant difference was observed in phosphorylated-STAT3/total-STAT3 expression between the adropin and SI/R groups and Janus kinase 2 inhibitor AG490 did not significantly inhibit the protective role of adropin. These results indicate that adropin exerts a protective effect against SI/R injury through the RISK pathway instead of the survivor activating factor enhancement pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly, SB202190 / Amgen, PD98059 / Wayne State University
Journal: Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells. (Pubmed Central) - Oct 11, 2019
Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.
- |||||||||| quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal: Distinct Roles of Small GTPases Rac1 and Rac2 in Histamine H4 Receptor-Mediated Chemotaxis of Mast Cells. (Pubmed Central) - Oct 9, 2019
Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) by LY294002 suppressed the histamine-induced chemotaxis and activation of Rac GTPases, suggesting that PI3K regulates chemotaxis upstream of Rac activation...Downregulation of Rac1 and Rac2 led to attenuated response in calcium mobilization and ERK activation, respectively. These observations suggested that Rac1 and Rac2 have distinct and essential roles in intracellular signaling downstream of H receptor-PI3K in histamine-induced chemotaxis of mast cells.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection. (Pubmed Central) - Oct 8, 2019
HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Overcoming Target Driven Fratricide for T Cell Therapy. (Pubmed Central) - Oct 8, 2019
The first focused upon the inclusion of a Phosphoinositol-3-Kinase inhibitor (LY294002) into the production process...By means of targeted inhibition of NKG2D expression or generic inhibition of enzyme function, target-driven CAR T fratricide can be overcome. These strategies have been incorporated into on-going clinical trials to enable a highly efficient and reproducible manufacturing process for NKG2D-CAR T cells.
- |||||||||| quercetin (LY294002) / Eli Lilly, propranolol / Generic Mfg.
Journal: Norepinephrine upregulates volume-regulated chloride current by PKA-independent cAMP/Epac pathway in human atrial myocytes. (Pubmed Central) - Oct 4, 2019
These data support the novel concept that I evoked by cell swelling of human atrial myocytes is upregulated by norepinephrine via a PKA-independent cAMP/Epac pathway in human atrial myocytes. Cyclic AMP/Epac-induced I is expected to shorten action potential duration during human atrial myocytes swelling and may be involved in abnormal cardiac electrical activity during cardiac pathologies that evoke β-adrenergic signaling.
- |||||||||| quercetin (LY294002) / Eli Lilly
Biomarker, Journal: Adenine decreases hypertrophic effects through interleukin-18 receptor. (Pubmed Central) - Oct 4, 2019
After treatment with inhibitors SB203580 and LY294002, the levels of p38 MAPK and PI3 kinase, respectively, decreased along with cell size and IL-18R expression...In this study, IL-18 induced cardiomyoblast hypertrophy through IL-18R upregulation, which was found to be related to p38 MAPK and PI3 kinase signaling. Adenine, but not AuNPs, showed antihypertrophic effects possibly because of decreased levels of signaling.
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