Search results for: DiscoveryPak™ Receptor Tyrosine Kinase (RTK) Inhibitor Set
#28852500 2017/08/30 Save this To Up
Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique metabolic changes in cancer progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), and MET receptor are highly expressed in TNBC, making both promising therapeutic targets. RTK signaling profoundly alters cellular metabolism by increasing glucose consumption and subsequently diverting glucose carbon sources into metabolic pathways necessary to support the tumorigenesis. Therefore, detailed metabolic profiles of TNBC subtypes and their response to tyrosine kinase inhibitors may identify therapeutic sensitivities.
2619 related Products with: Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.Breast cancer membrane pr Nycodenz, non ionic, non Breast cancer (multiple t Breast cancer tissue arra Breast cancer (IDC) tissu Breast cancer and adjacen Breast cancer tissue arra Breast cancer tissue arra Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer and matched
#28453458 2017/04/28 Save this To Up
Reduced EphB6 protein in gastric carcinoma and associated lymph nodes suggests EphB6 as a gastric tumor and metastasis inhibitor.Eph receptors comprise the largest group of the receptor tyrosine kinase (RTK) family, and Eph receptors interacting with their ligand ephrins play an important role in development and tumorigenesis. EphB6, a special Eph receptor that lacks tyrosine kinase activity, was reported to be expressed in some human cancers. The clinical significance of EphB6 in gastric carcinoma has not been well investigated.
2968 related Products with: Reduced EphB6 protein in gastric carcinoma and associated lymph nodes suggests EphB6 as a gastric tumor and metastasis inhibitor.Breast fibroadenoma tissu Breast cancer tissue arra Tissue array of breast ca Breast cancer, carcinoma Tissue array of breast ca Colorectal carcinoma and GI cancer (esophageal, ga Tissue array of gastritis Gastric carcinoma, gastri EMAP-II Inhibitor Z-ASTD- EMAP-II Inhibitor Z-ASTD- EMAP II Inhibitor Z ASTD
#27450453 2016/09/16 Save this To Up
JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies.Resistance limits the effectiveness of receptor tyrosine kinase (RTK)-targeted therapies. Combination therapies targeting resistance mechanisms can considerably improve response, but will require an improved understanding of when particular combinations will be effective. One common form of resistance is bypass signaling, wherein RTKs not targeted by an inhibitor can direct reactivation of pathways essential for survival. Although this mechanism of resistance is well appreciated, it is unclear which downstream signaling events are responsible. Here, we apply a combined experimental- and statistical modeling-based approach to identify a set of pathway reactivation essential for RTK-mediated bypass resistance. Differences in the downstream pathway activation provided by particular RTKs lead to qualitative differences in the capacity of each receptor to drive therapeutic resistance. We identify and validate that the JNK pathway is activated during and strongly modulates bypass resistance. These results identify effective therapeutic combinations that block bypass-mediated resistance and provide a basic understanding of this network-level change in kinase dependence that will inform the design of prognostic assays for identifying effective therapeutic combinations in individual patients. Cancer Res; 76(18); 5219-28. ©2016 AACR.
2732 related Products with: JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies.AP-1 Reporter – HEK293 PathwayReady™ EGFR Sign anti-EGFR (Phospho-Tyr119 Human Mouse Rat Phospho-E Human Phospho-EGFR (Y1045 Human Phospho-EGFR (Y1068 Human Phospho-EGFR (Y1086 Human Phospho-EGFR (Y992) Topoisomerase II; Clone Topoisomerase II; Clone Topoisomerase II; Clone Toludine Blue Solution
#27429073 2016/07/19 Save this To Up
Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy.Aberrant fibroblast growth factor receptor (FGFR) activation/expression is a common feature in lung cancer (LC). In this study, we evaluated the antitumor activity of and the mechanisms underlying acquired resistance to two potent selective FGFR inhibitors, AZD4547 and BAY116387, in LC cell lines. The antitumor activity of AZD4547 and BAY1163877 was screened in 24 LC cell lines, including 5 with FGFR1 amplification. Two cell lines containing FGFR1 amplifications, H1581 and DMS114, were sensitive to FGFR inhibitors (IC50<250 nm). Clones of FGFR1-amplified H1581 cells resistant to AZD4547 or BAY116387 (H1581AR and H1581BR cells, respectively) were established. Receptor tyrosine kinase (RTK) array and immunoblotting analyses showed strong overexpression and activation of Met in H1581AR/BR cells, compared with that in the parental cells. Gene set enrichment analysis against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed that cytokine-cytokine receptor interaction pathways were significantly enriched in H1581AR/BR cells, with Met contributing significantly to the core enrichment. Genomic DNA quantitative PCR and fluorescent in situ hybridization analyses showed MET amplification in H1581AR, but not in H1581BR, cells. Met amplification drives acquired resistance to AZD4547 in H1581AR cells by activating ErbB3. Combination treatment with FGFR inhibitors and an anaplastic lymphoma kinase (ALK)/Met inhibitor, crizotinib, or Met-specific short interfering RNA (siRNA) synergistically inhibited cell proliferation in both H1581AR and H1581BR cells. Conversely, ectopic expression of Met in H1581 cells conferred resistance to AZD4547 and BAY1163877. Acquired resistance to FGFR inhibitors not only altered cellular morphology, but also promoted migration and invasion of resistant clones, in part by inducing epithelial-to-mesenchymal transition. Taken together, our data suggest that Met activation is sufficient to bypass dependency on FGFR signaling. Concurrent inhibition of the Met and FGFR pathways may have synergistic clinical benefits when targeting FGFR-dependent LC.
2788 related Products with: Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy.Lung cancer tissue array Lung cancer tissue array, Lung cancer tissue array Colon cancer, metastasize Mid advanced stage bladde Breast cancer and matched Breast cancer and matched Breast cancer and matched Breast cancer, carcinoma Middle advanced stage bre Middle advanced stage bre Colon cancer and lung can
#23028479 2012/10/02 Save this To Up
Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma.To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy.
1186 related Products with: Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma.Epidermal Growth Factor ( Epidermal Growth Factor ( IGF-1R Signaling Phospho- Lung adenocarcinoma and n Mouse AntiMer Receptor Ty DiscoveryPak™ Receptor Epidermal Growth Factor ( Epidermal Growth Factor ( TCGF (Natural T Cell Grow Human Insulin-like Growth Human Epidermal Growth Fa Human Insulin-like Growth
#22120714 2012/08/09 Save this To Up
Regulation of lipid binding underlies the activation mechanism of class IA PI3-kinases.Somatic missense mutations in PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinases, occur frequently in human cancers. Activating mutations spread across multiple domains, some of which are located at inhibitory contact sites formed with the regulatory subunit p85α. PIK3R1, which encodes p85α, also has activating somatic mutations. We find a strong correlation between lipid kinase and lipid-binding activities for both wild-type (WT) and a representative set of oncogenic mutant complexes of p110α/p85α. Lipid binding involves both electrostatic and hydrophobic interactions. Activation caused by a phosphorylated receptor tyrosine kinase (RTK) peptide binding to the p85α N-terminal SH2 domain (nSH2) induces lipid binding. This depends on the polybasic activation loop as well as a conserved hydrophobic motif in the C-terminal region of the kinase domain. The hotspot E545K mutant largely mimics the activated WT p110α. It shows the highest basal activity and lipid binding, and is not significantly activated by an RTK phosphopeptide. Both the hotspot H1047R mutant and rare mutations (C420R, M1043I, H1047L, G1049R and p85α-N564D) also show increased basal kinase activities and lipid binding. However, their activities are further enhanced by an RTK phosphopeptide to levels markedly exceeding that of activated WT p110α. Phosphopeptide binding to p110β/p85α and p110δ/p85α complexes also induces their lipid binding. We present a crystal structure of WT p110α complexed with the p85α inter-SH2 domain and the inhibitor PIK-108. Additional to the ATP-binding pocket, an unexpected, second PIK-108 binding site is observed in the kinase C-lobe. We show a global conformational change in p110α consistent with allosteric regulation of the kinase domain by nSH2. These findings broaden our understanding of the differential biological outputs exhibited by distinct types of mutations regarding growth factor dependence, and suggest a two-tier classification scheme relating p110α and p85α mutations with signalling potential.
2783 related Products with: Regulation of lipid binding underlies the activation mechanism of class IA PI3-kinases.Ofloxacin CAS Number [824 ELISA Binding Buffer ELISA Binding Buffer ELISA Binding Buffer IÃŽÂºB â„¢ IÃŽÂºB â„¢ (DN) IAPP mutant Acyl CoA binding Protein Actin binding EGFP E. coli SSB (Single Stran E. coli SSB (Single Stran E. coli SSB (Single Stran
#17293140 2007/07/02 Save this To Up
3D QSAR studies on a series of potent and high selective inhibitors for three kinases of RTK family.For targets belonging to the same family of receptors, inhibitors often act at more than one biological target and produce a synergistic effect. Separate CoMFA and CoMSIA models were developed from our data set for the KDR, cKit and Tie-2 inhibitors. These models showed excellent internal predictability and consistency, and validation using test-set compounds yielded a good predictive power for the pIC(50) value. The field contour maps (CoMFA and CoMSIA) corresponding to the KDR, cKit and Tie-2 kinase subtypes reflected the characteristic similarities and differences between these types. These maps provided valuable information to facilitate structural modifications of the inhibitor to increase selectivity for the KDR over cKit and Tie-2.
2082 related Products with: 3D QSAR studies on a series of potent and high selective inhibitors for three kinases of RTK family.RAP2C, member of RAS onco EGF Phospho-Specific Arra EnzyChrom™ Kinase Assay Cytokeratin, High Molecu Cytokeratin, High Molecu Cytokeratin, High Molecu HBV surface recombinant a MOUSE ANTI BOVINE ROTAVIR Bone Morphogenetic Protei Growth Differentiation Fa Amplite™ Fluorimetric F Caspase-Family Inhibitor
#16885344 2006/08/03 Save this To Up
ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice.Glioblastoma multiforme is the most common and lethal form of primary brain cancer. Diagnosis of this advanced glioma has a poor prognosis due to the ineffectiveness of current therapies. Aberrant expression of receptor tyrosine kinases (RTK) in glioblastoma multiformes is suggestive of their role in initiation and maintenance of these tumors of the central nervous system. In fact, ectopic expression of the orphan RTK ROS is a frequent event in human brain cancers, yet the pathologic significance of this expression remains undetermined. Here, we show that a glioblastoma-associated, ligand-independent rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse. We show that this FIG-ROS-mediated tumor formation in vivo parallels the activation of the tyrosine phosphatase SH2 domain-containing phosphatase-2 (SHP-2) and a phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling axis in tumors and tumor-derived cell lines. We have established a fully penetrant preclinical model for adult onset of glioblastoma multiforme in keeping with major genetic events observed in the human disease. These findings provide novel and important insights into the role of ROS and SHP-2 function in solid tumor biology and set the stage for preclinical testing of targeted therapeutic approaches.
1417 related Products with: ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice.Tyrosine Kinase Adaptors Mouse AntiMer Receptor Ty Aurora Kinase B Inhibitor Aurora Kinase B Inhibitor Aurora Kinase B Inhibitor Aurora Kinase B Inhibitor ATM Kinase Inhibitor ATM Kinase Inhibitor, KU- ATM Kinase Inhibitor, KU- Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri Mouse ALK tyrosine kinase
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