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PROTEIN-TYROSINE KINASE --- TYRPHOSTINS --- PROTEIN-TYROSINE KINASE --- TYRPHOSTINS
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Despite the existence of tumor-infiltrating T lymphocytes (TILs), the tumor manages to grow. The host laboratory has found that these TILs have dysfunctional cytokine secretion and lytic capacities. Treating TIL with a galectin antagonist can partially correct these defects. Galectins are lectins secreted in the tumor environment by tumor cells and macrophages. They bind to polysaccharide motifs that decorate the cell surface receptors. They can form galectin-glycoprotein lattices, wich decrease the mobility of these receptors. The host laboratory thought that TIL covered galectins had a poor ability to be activated. The Lck kinase is known to interact with both glycoproteins CD45 and LFA-1 expressed at the T cell surface. LFA-1 is an adhesion molecule involved in stabilizing intercellular interactions and the CD45 phosphatase is involved in the regulation of intracellular signaling. The host laboratory observed a lack of motility of these two receptors at the contact area between a TIL and its target, lack of motility that could be corrected by a treatment with galectin antagonists. We made preliminary experiments to trap CD45 and LFA-1 in artificial lattices by capturing these surface receptors with cross-linked anti-FLA-1 and anti-CD45 antibodies. These artificial lattices should reduce the motility of these receptors and mimic galectin- glycoprotein lattices. It will then be possible to examine whether this lack of receptor motility disrupt the secretion of cytokines by T lymphocytes as do galectins in TILs.
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A gripping business narrative and scientific thriller about what it takes to bring a wonder drug to market--and save countless lives.
Protein-tyrosine kinase --- Cancer --- Drug development --- Biotechnology industries --- Inhibitors --- Therapeutic use. --- Chemotherapy.
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Protein kinases function as components of signal transduction pathways, playing a central role in the control of cell growth, metabolism, differentiation, and apoptosis. The development of selective protein tyrosine kinase (PTK) inhibitors that can block or modulate diseases, such as cancer, with abnormalities in these signaling pathways is considered a promising approach for drug development. Currently, more than 20 different PTKs are being considered as potential therapeutic targets in oncology. In Protein Tyrosine Kinases: From Inhibitors to Useful Drugs, leading researchers from the Novartis group that pioneered Gleevec/Glivec™ and from around the world comprehensively survey the state-of-the-art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made toward generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing PTK inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors. Authoritative and state-of-the-art, Protein Tyrosine Kinases: From Inhibitors to Useful Drugs details the key stages in the design of PTK inhibitors and their development into useful drugs.
Protein-Tyrosine Kinase --- Lymphocyte Specific Protein Tyrosine Kinase p56(lck) --- Neoplasms --- src-Family Kinases --- Protein-tyrosine kinase --- Cancer --- physiology. --- drug therapy. --- Inhibitors --- Therapeutic use. --- Chemotherapy. --- Chimiothérapie --- Cancer -- Chemotherapy. --- Protein-tyrosine kinase -- Inhibitors -- Therapeutic use. --- Biology --- Medicine --- Chemistry --- Physical Sciences & Mathematics --- Health & Biological Sciences --- Biochemistry --- Cytology --- Oncology --- Biology - General --- Therapeutic use --- Chemotherapy --- Hydroxyaryl-protein kinase --- Tyrosine kinase --- Tyrosine protein kinase --- Tyrosine-specific protein kinase --- Tyrosylprotein kinase --- Life sciences. --- Biochemistry. --- Life Sciences. --- Biochemistry, general. --- Protein kinases --- Antineoplastic agents --- Treatment
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Mental illness --- Treatment. --- Psychiatry --- Protein-tyrosine kinase --- Nervous system --- Receptor Protein-Tyrosine Kinases --- Nerve Degeneration --- Mental Disorders --- Receptors. --- Degeneration --- therapy
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Abl Family Kinases in Development and Disease provides an overview of the functions of Abl family kinases in Development and Disease. This new title discusses the biochemical, genetic, and cell biological data that elucidate the cellular roles for these kinases in these processes.
Protein-tyrosine kinase. --- Protein-tyrosine kinase --- Pathophysiology. --- Hydroxyaryl-protein kinase --- Tyrosine kinase --- Tyrosine protein kinase --- Tyrosine-specific protein kinase --- Tyrosylprotein kinase --- Protein kinases --- Neurosciences. --- Oncology. --- Human physiology. --- Cancer Research. --- Human Physiology. --- Human biology --- Medical sciences --- Physiology --- Human body --- Tumors --- Neural sciences --- Neurological sciences --- Neuroscience --- Nervous system --- Cancer research. --- Cancer research
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PHOSPHODIESTERASE TYPE IV INHIBITORS --- CYCLOSPORINS --- CARBAPENEM ANTIBIOTICS --- AROMATASE (INHIBITION) --- RISPERIDONE AND RELATED 5HT2/D2 ANTAGONISTS --- ANTIPSYCHOTIC AGENTS --- PROTEIN TYROSINE KINASE INHIBITORS --- SQUALENE SYNTHASE INHIBITORS --- HYPOCHOLESTEROLAEMIC AGENTS --- BIOSYNTHESIS AND MECHANISM OF ACTION --- PHOSPHODIESTERASE TYPE IV INHIBITORS --- CYCLOSPORINS --- CARBAPENEM ANTIBIOTICS --- AROMATASE (INHIBITION) --- RISPERIDONE AND RELATED 5HT2/D2 ANTAGONISTS --- ANTIPSYCHOTIC AGENTS --- PROTEIN TYROSINE KINASE INHIBITORS --- SQUALENE SYNTHASE INHIBITORS --- HYPOCHOLESTEROLAEMIC AGENTS --- BIOSYNTHESIS AND MECHANISM OF ACTION
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The volume will serve as a primer on tyrosine kinase signaling and its importance in cancer. The volume will first introduce the common denominators of small-molecule and antibody-derived inhibitors, as well as the general phenomenon of resistance. The volume will then detail resistance to the most commonly used classes of tyrosine kinase inhibitors, and will focus specific chapters on resistance to BCR-ABL1, FLT3, angiokinase family members, and ALK inhibitors.
Medicine. --- Cancer research. --- Biomedicine. --- Cancer Research. --- Protein-tyrosine kinase --- Cancer --- Inhibitors --- Therapeutic use. --- Chemotherapy. --- Hydroxyaryl-protein kinase --- Tyrosine kinase --- Tyrosine protein kinase --- Tyrosine-specific protein kinase --- Tyrosylprotein kinase --- Antineoplastic agents --- Protein kinases --- Treatment --- Oncology. --- Tumors --- Cancer research
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