Sentences with phrase «with kinase inhibitors»

Cells were pretreated with kinase inhibitors for 1 h, followed by treatment with ActD for 6 h in HepG2 cells.

This visual abstract depicts how Wei et al. utilize single - cell phosphoproteomic analysis of patient derived glioblastoma models to identify shifts in signaling coordination following short - term treatment with kinase inhibitors, which facilitates the design of combination therapy approaches with reduced resistance and improved efficacy.

When the cells were treated with each kinase inhibitor individually, the applied kinase inhibitors themselves caused a minor induction of p53 expression (Fig. 5).

Not exact matches

The authors also found that a novel small molecule inhibitor of the salvage pathway enzyme deoxycytidine kinase blocked leukemia growth in mice in combination with thymidine (to inhibit the de novo pathway).

Therefore, a novel therapeutic approach in inflammatory breast cancer could involve a combination of conventional chemotherapy with small - molecule inhibitors of the Cdk2 cell cycle kinase.

«We've crossed the Rubicon with respect to kinase inhibitors,» he says.

And none of these kinase inhibitors have yet been rigorously tested in a head - to - head comparison with the protein therapies already on the market.

The estimation of EGFR mutation status is essential for the identification of non-small cell lung carcinoma (NSCLC) patients who may benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs), and hence for improving therapeutic efficacy.

One of the more intriguing findings in the study was that increasing histone crotonylation works synergistically with other known anti-HIV latency molecules, such as the protein kinase C agonist PEP005 and the HDAC inhibitor vorinostat.

For example, epidermal growth factor (EGFR) mutations may result in sensitivity to drugs that are EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib or gefitinib, whereas individuals with the EGFR T790M mutation are more resistant to these drugs.

They looked at other genes that interacted with TAK1 kinase including activators and inhibitors of the TAK1 pathway and found that most of them also affected regeneration, but only when worms were infected.

EGFR tyrosine kinase inhibitor (TKI) therapy is approved for EGFR activating mutation positive patients with advanced NSCLC, but the standard for determining mutation status is with DNA derived directly from tumor tissue, which can be limited or not available.

Among patients with advanced non-small cell lung cancer without a mutation of a certain gene (EGFR), conventional chemotherapy, compared with treatment using epidermal growth factor receptor tyrosine kinase inhibitors, was associated with improvement in survival without progression of the cancer, but not with overall survival, according to a study in the April 9 issue of JAMA.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred treatment option for patients with advanced non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene.

DDRs inhibition with a tyrosine kinase inhibitor appears to insulate the brain via blood - brain barrier repair, which prevents harmful immune cells that circulate in the body from getting into the brain where they can indiscriminately attack and kill healthy and sick neurons, like those that have been unable to perform autophagy to «take out their trash,» says Moussa.

«Patients with non-small cell lung cancer (NSCLC) should receive front line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib,» said lead author Professor Giorgio Scagliotti, head of the Department of Oncology, University of Turin, Italy.

The Structural Genomics Consortium at the University of North Carolina at Chapel Hill (SGC - UNC), in partnership with the DiscoverX Corporation, has reached the milestone halfway point in its development of the Kinase Chemogenomic Set, a potent group of inhibitors which allow deeper exploration of the human kinome, a family of enzymes critical to understanding human disease and developing new therapies.

Approximately 10 - 15 % of Caucasian and 30 - 35 % of Asian patients with NSCLC have a mutation in the epidermal growth factor receptor (EGFR), which can be successfully targeted with EGFR inhibitors called tyrosine kinase inhibitors (TKI), such as erlotinib, gefitinib and afatinib.

«Through our collaboration with DiscoverX, we screened a large set of compounds that we call Published Kinase Inhibitor Set 2, and these results allowed us to reach the halfway point in constructing the KCGS» said David Drewry, a research associate professor at the UNC Eshelman School of Pharmacy and SGC - UNC principal investigator who is leading the project to develop the Kinase Chemogenomic Set.

If this is true, then immunocheckpoint blockade combination with EGFR tyrosine kinase inhibitors is a major path towards improving outcome of patients who have EGFR - mutant non-small-cell lung cancer.»

In a proof - of - concept study, Fourches and Ash looked at the ERK2 kinase — an enzyme associated with several types of cancer — and a group of 87 known ERK2 inhibitors, ranging from very active to inactive.

We used the janus kinase (JAK) inhibitor baricitinib with IFN - blocking activity in vitro, to ameliorate disease.

A class of oral specialty drugs, tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of CML, largely transforming it into a chronic condition and enabling many patients to have a near - normal lifespan, particularly when compared to a median survival of less than three years with prior therapies.

Scanning electron micrograph of the coronary microvasculature of a mouse that has been treated with a small molecule tyrosine kinase inhibitor of platelet - derived growth factor receptor beta.

This lab, in collaboration with the lab of Ruben Shaw at the Salk Institute, recently identified SBI - 0206965, the first potent and selective small molecule inhibitor of ULK1, a serine / threonine kinase that is a critical regulator of autophagy.

A combination of the FLT3 kinase inhibitor quizartinib with 5 - azacitidine or low - dose cytarabine is active in patients with FLT3 - ITD mutated myeloid leukemias, according to a new study.

Glennie et al 134 have shown that T cells stimulated in co-cultures with MSC exhibit an extensive inhibition of cyclin D2 and upregulation of the cyclin dependent kinase inhibitor p27kip1.

A combination of the FLT3 kinase inhibitor quizartinib with 5 - azacitidine (AZA) or low - dose cytarabine (LDAC) is active in patients with FLT3 - ITD mutated myeloid leukemias, according to a new study.

Another focus was the differential sensitivity of different mutations towards inhibition with specific tyrosine kinase inhibitors (5).

Clathrin complexes with the inhibitor kappa B kinase signalosome: imaging the interactome.

It is known that one of the pathways involved in cutaneous cancer is mediated through CDKN2A which is a gene associated with melanoma dysregulation through its pro-oncogenic products p16INK4a (Cyclin - Dependent Kinase Inhibitor P16) and p14ARF (P14 alternate open reading frame)[28].

Larotrectinib, a highly selective inhibitor of all three tropomyosin receptor kinase (TRK) proteins, was recently shown to have marked and sustained antitumor activity in patients with TRK fusion — positive cancers, according to an analysis of three phase I and II cohorts.

Patients with chronic myeloid leukemia in the blast phase pose a significant therapeutic challenge and have poor survival, even in the tyrosine kinase inhibitor era, according to a new study.

Senderowicz AM, Headlee D, Stinson SF, et al: Phase I trial of continuous infusion flavopiridol, a novel cyclin - dependent kinase inhibitor, in patients with refractory neoplasms.

Similarly, inhibiting ABL kinase activity with the allosteric inhibitor GNF5 decreased TAZ protein abundance (fig.

The US Food and Drug Administration (FDA) recently approved the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib for the treatment of patients with relapsed or refractory marginal zone lymphoma who require systemic therapy and have had at least one prior anti-CD20 therapy.

Here we use a chemical genetics approach using knock - in mice in which either p38alpha or p38beta kinase has been rendered resistant to the effects of specific inhibitors along with p38beta knock - out mice to dissect the biological function of these specific kinase isoforms.

Currently, 31 tyrosine kinase inhibitors are FDA approved for human therapy, with many more in clinical trials.

The allosteric inhibitors specific for ABL kinases (which are currently in clinical trials) provide a potentially useful tool for selectively targeting ABL kinases in metastatic breast cancer types with an increase in the ABL pathway signature (58).

Moreover, we found that treatment with a selective allosteric inhibitor of the ABL kinases or simultaneous depletion of both ABL kinases in breast cancer cells impaired breast cancer bone metastases and decreased osteoclast activation in vitro and osteolysis in vivo.

Vorinostat interferes with the signaling transduction pathway of T - cell receptor and synergizes with phosphoinositide - 3 kinase inhibitors in cutaneous T - cell lymphoma

Along the same lines, in non-small cell lung cancer (NSCLC), acquired resistance to Gefitinib / Erlotinib kinase inhibitors has also been associated with a secondary mutation of the gatekeeper Thr790 residue of the epidermal growth factor receptor (EGFR).

These mutant kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine kinase are the most common genetic event in acute myeloid leukemia (AML), and specific inhibitors of the FMS - like tyrosine kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.

We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen - coated plates with a glycogen synthase kinase 3β inhibitor.

To visualize the Phe958 to Val mutation, we used the crystal structure of the JAK1 kinase domain with CMP6 inhibitor (Figure 2C).

It is likely that our RIPK2 inhibitor 1 may interfere with the kinase activity of these off targets indirectly by resolving the inflammation.

Conversely, JAK inhibitors did not affect MAP kinase - dependent proliferation of control autonomous cells transfected with an activated mutant of M - RAS.

Stephen Alexander, UK - Cannabinoid receptors, transporters, endocannabinoid turnover, hydrogen sulphide turnover Arthur Christopoulos, Australia (GPCRs Liaison)- G protein - coupled receptors; analytical pharmacology; allosteric modulation; biased agonism; drug discovery; neuropharmacology John Cidlowski, USA (NHRs Liaison)- Glucocorticoid receptor signaling; apoptosis and the immune system Anthony P. Davenport, UK (Chair Evolving Pharmacology, GPCRs Liaison) Doriano Fabbro, Switzerland - Kinases and their biology, kinase inhibitors, drug discovery, pharmacology of drugs (kinase inhibitors) in the indication oncology, biology of oncology Kozo Kaibuchi, Japan Yoshikatsu Kanai, Japan - Transporters, amino acid signals, epithelial function, cancer biology Francesca Levi - Schaffer, Israel - eosinophils and mast cells as effector cells in allergic inflammation: characterization of new receptors / ligands, hypoxia / angiogenesis and eosinophils, asthma, atopic dermatitis, allergic rhinitis, immunopharmacological modulation of allergic diseases by bispecific recombinant antibodies, bacteria interactions with eosinophils and mast cells, the allergic effector unit, mast cell derived tumors: new antibody based treatment, the allergic inflammation and the resolvome, non IgE - mediated mast cell activation in diseases Eliot H. Ohlstein, USA (Editor)- Drug discovery and development, urogenital biology, cardiovascular / metabolic medicine John A. Peters, UK (LGICs Liaison) Alex Phipps, UK - Oncology, Clinical Pharmacology, Biologics and Immunotherapy Joerg Striessnig, Austria (VGICs Liaison)- Physiology, pharmacology and pathophysiological role of voltage-gated calcium channels

Susan Amara, USA - «Regulation of transporter function and trafficking by amphetamines, Structure - function relationships in excitatory amino acid transporters (EAATs), Modulation of dopamine transporters (DAT) by GPCRs, Genetics and functional analyses of human trace amine receptors» Tom I. Bonner, USA (Past Core Member)- Genomics, G protein coupled receptors Michel Bouvier, Canada - Molecular Pharmacology of G protein - Coupled Receptors; Molecular mechanisms controlling the selectivity and efficacy of GPCR signalling Thomas Burris, USA - Nuclear Receptor Pharmacology and Drug Discovery William A. Catterall, USA (Past Core Member)- The Molecular Basis of Electrical Excitability Steven Charlton, UK - Molecular Pharmacology and Drug Discovery Moses Chao, USA - Mechanisms of Neurotophin Receptor Signaling Mark Coles, UK - Cellular differentiation, human embryonic stem cells, stromal cells, haematopoietic stem cells, organogenesis, lymphoid microenvironments, develomental immunology Steven L. Colletti, USA Graham L Collingridge, UK Philippe Delerive, France - Metabolic Research (diabetes, obesity, non-alcoholic fatty liver, cardio - vascular diseases, nuclear hormone receptor, GPCRs, kinases) Sir Colin T. Dollery, UK (Founder and Past Core Member) Richard M. Eglen, UK Stephen M. Foord, UK David Gloriam, Denmark - GPCRs, databases, computational drug design, orphan recetpors Gillian Gray, UK Debbie Hay, New Zealand - G protein - coupled receptors, peptide receptors, CGRP, Amylin, Adrenomedullin, Migraine, Diabetes / obesity Allyn C. Howlett, USA Franz Hofmann, Germany - Voltage dependent calcium channels and the positive inotropic effect of beta adrenergic stimulation; cardiovascular function of cGMP protein kinase Yu Huang, Hong Kong - Endothelial and Metabolic Dysfunction, and Novel Biomarkers in Diabetes, Hypertension, Dyslipidemia and Estrogen Deficiency, Endothelium - derived Contracting Factors in the Regulation of Vascular Tone, Adipose Tissue Regulation of Vascular Function in Obesity, Diabetes and Hypertension, Pharmacological Characterization of New Anti-diabetic and Anti-hypertensive Drugs, Hypotensive and antioxidant Actions of Biologically Active Components of Traditional Chinese Herbs and Natural Plants including Polypehnols and Ginsenosides Adriaan P. IJzerman, The Netherlands - G protein - coupled receptors; allosteric modulation; binding kinetics Michael F Jarvis, USA - Purines and Purinergic Receptors and Voltage-gated ion channel (sodium and calcium) pharmacology Pain mechanisms Research Reproducibility Bong - Kiun Kaang, Korea - G protein - coupled receptors; Glutamate receptors; Neuropsychiatric disorders Eamonn Kelly, Prof, UK - Molecular Pharmacology of G protein - coupled receptors, in particular opioid receptors, regulation of GPCRs by kinasis and arrestins Terry Kenakin, USA - Drug receptor pharmacodynamics, receptor theory Janos Kiss, Hungary - Neurodegenerative disorders, Alzheimer's disease Stefan Knapp, Germany - Rational design of highly selective inhibitors (so call chemical probes) targeting protein kinases as well as protein interaction inhibitors of the bromodomain family Andrew Knight, UK Chris Langmead, Australia - Drug discovery, GPCRs, neuroscience and analytical pharmacology Vincent Laudet, France (Past Core Member)- Evolution of the Nuclear Receptor / Ligand couple Margaret R. MacLean, UK - Serotonin, endothelin, estrogen, microRNAs and pulmonary hyperten Neil Marrion, UK - Calcium - activated potassium channels, neuronal excitability Fiona Marshall, UK - GPCR molecular pharmacology, structure and drug discovery Alistair Mathie, UK - Ion channel structure, function and regulation, pain and the nervous system Ian McGrath, UK - Adrenoceptors; autonomic transmission; vascular pharmacology Graeme Milligan, UK - Structure, function and regulation of G protein - coupled receptors Richard Neubig, USA (Past Core Member)- G protein signaling; academic drug discovery Stefan Offermanns, Germany - G protein - coupled receptors, vascular / metabolic signaling Richard Olsen, USA - Structure and function of GABA - A receptors; mode of action of GABAergic drugs including general anesthetics and ethanol Jean - Philippe Pin, France (Past Core Member)- GPCR - mGLuR - GABAB - structure function relationship - pharmacology - biophysics Helgi Schiöth, Sweden David Searls, USA - Bioinformatics Graeme Semple, USA - GPCR Medicinal Chemistry Patrick M. Sexton, Australia - G protein - coupled receptors Roland Staal, USA - Microglia and neuroinflammation in neuropathic pain and neurological disorders Bart Staels, France - Nuclear receptor signaling in metabolic and cardiovascular diseases Katerina Tiligada, Greece - Immunopharmacology, histamine, histamine receptors, hypersensitivity, drug allergy, inflammation Georg Terstappen, Germany - Drug discovery for neurodegenerative diseases with a focus on AD Mary Vore, USA - Activity and regulation of expression and function of the ATP - binding cassette (ABC) transporters

Because of robust off - target effects of most RIPK2 inhibitors, we carried out molecular modeling (docking) and cheminformatics analyses by carefully analyzing the only known crystal structure of RIPK2 in association with the c - ABL kinase inhibitor ponatinib (https://www.rcsb.org/pdb/explore/macroMoleculeData.do?structureId=4C8B).