Search results for: DiscoveryPak™ PI 3 Kinase Inhibitor Set
#28780388 2017/08/06 Save this To Up
Phosphatidylinositol 3 kinase (PI3K) modulates manganese homeostasis and manganese-induced cell signaling in a murine striatal cell line.In a recent study, we found that blocking the protein kinase ataxia telangiectasia mutated (ATM) with the small molecule inhibitor (SMI) KU-55933 can completely abrogate Mn-induced phosphorylation of p53 at serine 15 (p-p53) in human induced pluripotent stem cell (hiPSC)-differentiated striatal neuroprogenitors. However, in the immortalized mouse striatal progenitor cell line STHdh(Q7/Q7), a concentration of KU55933 far exceeding its IC50 for ATM was required to inhibit Mn-induced p-p53. This suggested an alternative signaling system redundant with ATM kinase for activating p53 in this cell line- one that was altered by KU55933 at these higher concentrations (i.e. mTORC1, DNApk, PI3K). To test the hypothesis that one or more of these signaling pathways contributed to Mn-induced p-p53, we utilized a set of SMIs (e.g. NU7441 and LY294002) known to block DNApk, PI3K, and mTORC1 at distinct concentrations. We found that the SMIs inhibit Mn-induced p-p53 expression near the expected IC50s for PI3K, versus other known targets. We hypothesized that inhibiting PI3K reduces intracellular Mn and thereby decreases activation of p53 by Mn. Using the cellular fura-2 manganese extraction assay (CFMEA), we determined that KU55933/60019, NU7441, and LY294002 (at concentrations near their IC50s for PI3K) all decrease intracellular Mn (∼50%) after a dual, 24-h Mn and SMI exposure. Many pathways are activated by Mn aside from p-p53, including AKT and mTOR pathways. Thus, we explored the activation of these pathways by Mn in STHdh cells as well as the effects of other pathway inhibitors. p-AKT and p-S6 activation by Mn is almost completely blocked upon addition of NU7441(5μM) or LY294002(7μM), supporting PI3K's upstream role in the AKT/mTOR pathway. We also investigated whether PI3K inhibition blocks Mn uptake in other cell lines. LY294002 exposure did not reduce Mn uptake in ST14A, Neuro2A, HEK293, MEF, or hiPSC-derived neuroprogenitors. Next, we sought to determine whether inhibition of PI3K blocked p53 phosphorylation by directly blocking an unknown PI3K/p53 interaction or indirectly reducing intracellular Mn, decreasing p-p53 expression. In-Cell Western and CFMEA experiments using multiple concentrations of Mn exposures demonstrated that intracellular Mn levels directly correlated with p-p53 expression with or without addition of LY294002. Finally, we examined whether PI3K inhibition was able to block Mn-induced p-p53 activity in hiPSC-derived striatal neuroprogenitors. As expected, LY294002 does not block Mn-induced p-p53 as PI3K inhibition is unable to reduce Mn net uptake in this cell line, suggesting the effect of LY294002 on Mn uptake is relatively specific to the STHdh mouse striatal cell line.
1363 related Products with: Phosphatidylinositol 3 kinase (PI3K) modulates manganese homeostasis and manganese-induced cell signaling in a murine striatal cell line.Cultrex96 Well 3D BME Cel AP-1 Reporter – HEK293 T-Cell Receptor Signaling Rabbit Anti-Cell death in Rabbit Anti-SF9 Insect Ce Rabbit Anti-Insect Cell L OxiSelect™ Cellular UV- anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl anti SLAM anti CDw150 IgG anti CD37 IgG2b (monoclon
#28574782 2017/06/02 Save this To Up
RNA-based ovarian cancer research from 'a gene to systems biomedicine' perspective.Ovarian cancer remains the leading cause of death from a gynecologic malignancy, and treatment of this disease is harder than any other type of female reproductive cancer. Improvements in the diagnosis and development of novel and effective treatment strategies for complex pathophysiologies, such as ovarian cancer, require a better understanding of disease emergence and mechanisms of progression through systems medicine approaches. RNA-level analyses generate new information that can help in understanding the mechanisms behind disease pathogenesis, to identify new biomarkers and therapeutic targets and in new drug discovery. Whole RNA sequencing and coding and non-coding RNA expression array datasets have shed light on the mechanisms underlying disease progression and have identified mRNAs, miRNAs, and lncRNAs involved in ovarian cancer progression. In addition, the results from these analyses indicate that various signalling pathways and biological processes are associated with ovarian cancer. Here, we present a comprehensive literature review on RNA-based ovarian cancer research and highlight the benefits of integrative approaches within the systems biomedicine concept for future ovarian cancer research. We invite the ovarian cancer and systems biomedicine research fields to join forces to achieve the interdisciplinary caliber and rigor required to find real-life solutions to common, devastating, and complex diseases such as ovarian cancer.
1251 related Products with: RNA-based ovarian cancer research from 'a gene to systems biomedicine' perspective.Top 10 cancer tissue arra Multiple organ cancer tis CA125, Ovarian Cancer An CA125, Ovarian Cancer An CA125, Ovarian Cancer An HIV 1 gag p24 recombinant Anti HIV 1 p24 Clone 39 5 MONOBODIES (Monoclonal An Anti HIV 1 p24 Clone 39 5 MONOBODIES (Monoclonal An YKL-39 antibody Source Ra Tom 40 Blocking Peptide;A
#28507556 2017/05/16 Save this To Up
Differential Effects of Phosphatidylinositol 4-Kinase (PI4K) and 3-Kinase (PI3K) Inhibitors on Stomatal Responses to Environmental Signals.Specific cellular components including products of phosphatidylinositol (PI) metabolism play an important role as signaling molecules in stomatal responses to environmental signals. In this study, pharmacological inhibitors of a set of cellular components, including PI4-kinase (PI4K) and PI3K, were used to investigate stomatal closure in response to CO2, darkness, and abscisic acid (ABA). Treatment with PAO, a specific inhibitor of PI4K, specifically inhibited the stomatal response to CO2 compared with that to darkness and ABA. In contrast, treatment with LY294002, a PI3K-specific inhibitor, specifically inhibited the stomatal response to darkness compared with that to CO2 and ABA. The specific inhibitory effects of PAO and LY294002 were also observed as changes in the spatial density of dot-like structures labeled by green fluorescent protein-tagged PATROL1, a protein that controls stomatal aperture possibly via regulation of H(+)-ATPase amount in guard cell plasma membranes. Our results suggest an important role for PI4K and PI3K in the CO2 and darkness signal transduction pathways, respectively, that mediate PATROL1 dynamics.
1612 related Products with: Differential Effects of Phosphatidylinositol 4-Kinase (PI4K) and 3-Kinase (PI3K) Inhibitors on Stomatal Responses to Environmental Signals.Primary antibody DRAK1 A Primary antibody DRAK2 A EnzyChrom™ Kinase Assay DiscoveryPak™ PI 3 Kina DiscoveryPak™ EGFR Tyro DiscoveryPak™ Receptor PathwayReady™ MAP Kinas Glycerol kinase p44 42 MAP Kinase p44 42 MAP Kinase (Phosph p70 S6 Kinase (Phospho Th p70 S6 Kinase
#28092667 2017/01/16 Save this To Up
Oncogenic BRAF fusions in mucosal melanomas activate the MAPK pathway and are sensitive to MEK/PI3K inhibition or MEK/CDK4/6 inhibition.Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.
2167 related Products with: Oncogenic BRAF fusions in mucosal melanomas activate the MAPK pathway and are sensitive to MEK/PI3K inhibition or MEK/CDK4/6 inhibition.AZD-6244 Mechanisms: MEK FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Oral squamous cell cancer Cell Meter™ Fluorimetri Directed In Vivo Angiogen AS-703026 Mechanisms: MEK RDEA-119 (BAY-869766) Mec CI-1040 (PD184352) Mechan RO-5126766 Mechanisms: Ra
#27378558 2016/08/01 Save this To Up
Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.
1014 related Products with: Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.(5α,16β)-N-Acetyl-16-[2 (5α,16β)-N-Acetyl-16-ac 5α-N-Acetyl-2'H-androst- 5α-N-Acetyl-2'H-androst- 3-O-Acetyl 5,14-Androstad 3-O-Acetyl-17-O-tert-buty 3β-O-Acetyl-androsta-5,1 Pfu DNA Polymerase protei Glucose 6 phosphate Trans Glucose Transporter 1 Glucose 6 phosphatase Carnitine O palmitoyltran
#27147735 2016/06/25 Save this To Up
Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis.The pathogenic Old World arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with a high rate of mortality in humans. Several LASV receptors, including dystroglycan (DG), TAM receptor tyrosine kinases, and C-type lectins, have been identified, suggesting complex receptor use. Upon receptor binding, LASV enters the host cell via an unknown clathrin- and dynamin-independent pathway that delivers the virus to late endosomes, where fusion occurs. Here we investigated the mechanisms underlying LASV endocytosis in human cells in the context of productive arenavirus infection, using recombinant lymphocytic choriomeningitis virus (rLCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that rLCMV-LASVGP entered human epithelial cells via DG using a macropinocytosis-related pathway independently of alternative receptors. Dystroglycan-mediated entry of rLCMV-LASVGP required sodium hydrogen exchangers, actin, and the GTPase Cdc42 and its downstream targets, p21-activating kinase-1 (PAK1) and Wiskott-Aldrich syndrome protein (N-Wasp). Unlike other viruses that enter cells via macropinocytosis, rLCMV-LASVGP entry did not induce overt changes in cellular morphology and hardly affected actin dynamics or fluid uptake. Screening of kinase inhibitors identified protein kinase C, phosphoinositide 3-kinase, and the receptor tyrosine kinase human hepatocyte growth factor receptor (HGFR) to be regulators of rLCMV-LASVGP entry. The HGFR inhibitor EMD 1214063, a candidate anticancer drug, showed antiviral activity against rLCMV-LASVGP at the level of entry. When combined with ribavirin, which is currently used to treat human arenavirus infection, EMD 1214063 showed additive antiviral effects. In sum, our study reveals that DG can link LASV to an unusual pathway of macropinocytosis that causes only minimal perturbation of the host cell and identifies cellular kinases to be possible novel targets for therapeutic intervention.
2211 related Products with: Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis.Recombinant Viral Antige West Nile Virus Pre M rec anti Adenovirus C11 IgG2a Viral antibodies, anti-R anti Rotavirus p42 IgG2a anti CD7 All T cells Reco anti Transferrin receptor Nrf antioxidant pathway A Cell cycle antibody array Cell Cycle Phospho-Specif T-Cell Receptor Signaling Primary Antibody Dropper
#27079001 2016/04/15 Save this To Up
[Establishment and Evaluation of Hypertensive Rat Model with Excessive Accumulation of Phlegm-dampness Syndrome].To observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.
2425 related Products with: [Establishment and Evaluation of Hypertensive Rat Model with Excessive Accumulation of Phlegm-dampness Syndrome].Rabbit Anti-Rat Androgen CAR,Car,Constitutive andr Ofloxacin CAS Number [824 Model 150 V T Ultrasonic ULTRASONIC HOMOGENIZERS: Model 300 V T Ultrasonic ULTRASONIC HOMOGENIZERS: Model 3000 Ultrasonic Hom ULTRASONIC HOMOGENIZERS: Amplite™ Fluorimetric G Amplite™ Fluorimetric G Androgen Receptor (Phosph
#25990325 2015/08/14 Save this To Up
FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21(Cip1/Waf1).Activity of FOXO (forkhead box O) transcription factors is inhibited by growth factor-PI3K (phosphoinositide 3-kinase)-PKB (protein kinase B)/Akt signalling to control a variety of cellular processes including cell cycle progression. Through comparative analysis of a number of microarray datasets we identified a set of genes commonly regulated by FOXO proteins and PI3K-PKB/Akt, which includes CTDSP2 (C-terminal domain small phosphatase 2). We validated CTDSP2 as a genuine FOXO target gene and show that ectopic CTDSP2 can induce cell cycle arrest. We analysed transcriptional regulation after CTDSP2 expression and identified extensive regulation of genes involved in cell cycle progression, which depends on the phosphatase activity of CTDSP2. The most notably regulated gene is the CDK (cyclin-dependent kinase) inhibitor p21(Cip1/Waf1) and in the present study we show that p21(Cip1/Waf1) is partially responsible for the cell cycle arrest through decreasing cyclin-CDK activity. Our data suggest that CTDSP2 induces p21(Cip1/Waf1) through increasing the activity of Ras. As has been described previously, Ras induces p21(Cip1/Waf1) through p53-dependent and p53-independent pathways and indeed both p53 and MEK inhibition can mitigate the CTDSP2-induced p21(Cip1/Waf1) mRNA up-regulation. In support of Ras activation by CTDSP2, depletion of endogenous CTDSP2 results in reduced Ras activity and thus CTDSP2 seems to be part of a larger set of genes regulated by FOXO proteins, which increase growth factor signalling upon FOXO activation.
2431 related Products with: FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21(Cip1/Waf1).Anti-p21 (WAF1, Cip1) Pur cell cycle progression 2 Cell Meter™ Generic Flu Cell Meter™ Generic Flu Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri FOXO3a Blocking Peptide;A Cell cycle antibody array Cell Cycle Control Phosph Cell Cycle Phospho-Specif Mouse Anti-Human p21 WAF1 Mouse AntiT cell receptor
#25931349 2015/05/01 Save this To Up
Pro-Apoptotic Activity of Ruxolitinib Alone and in Combination with Hydroxyurea, Busulphan, and PI3K/mTOR Inhibitors in JAK2-Positive Human Cell Lines.The JAK2V617F mutation plays a crucial role in the pathogenesis of myeloproliferative neoplasms (MPNs). Inhibition of JAK2 activity by ruxolitinib (RX) results in growth inhibition and apoptosis of cells carrying the JAK2V617F mutation however the exact mechanisms regulating apoptosis have not been fully elucidated.
1754 related Products with: Pro-Apoptotic Activity of Ruxolitinib Alone and in Combination with Hydroxyurea, Busulphan, and PI3K/mTOR Inhibitors in JAK2-Positive Human Cell Lines.CELLKINES Natural Human I Macrophage Colony Stimula Macrophage Colony Stimula Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri BEZ-235 Mechanisms: PI3K XL-765 (SAR-245409) Mecha GDC-0980 Mechanisms: PI3K BGT-226 Mechanisms: PI3K PKI-587 (PF-05212384) Mec PF-04691502 Mechanisms: P Rabbit Anti-Cell death in
#25588160 2015/02/27 Save this To Up
Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast cancer cells through the PI3K/AKT-mTOR pathway.To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC) cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and MCF-7 cells were incubated with 0.1 μmol/l gefitinib, 1 μmol/l gefitinib, 10 μmol/l gefitinib, 1 μmol/l SF1126, 0.1 μmol/l gefitinib+1 μmol/l SF1126, 1 μmol/l gefitinib+1 μmol/l SF1126, and 10 μmol/l gefitinib+1 μmol/l SF1126. Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors were detected by western blot. For TNBC cells, cell viability or survival was not significantly inhibited by gefitinib or SF1126 alone; however, marked cell apoptosis was noted in the gefitinib and SF1126 combination groups, and this effect was dose dependent. Also, the expressions of apoptosis markers, such as cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126 combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib combined with SF1126 could induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR-PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical trials of TNBC therapy by the combination of gefitinib and SF1126.
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