• Numerous TKIs aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti-tumor agents and anti-leukemic agents. (wikipedia.org)
  • Sunitinib, an inhibitor of the receptors for FGF, PDGF and VEGF is also based on early studies on TKIs aiming at VEGF receptors. (wikipedia.org)
  • Recently TKIs have been shown to deprive tyrosine kinases of access to the Cdc37-Hsp90 molecular chaperone system on which they depend for their cellular stability, leading to their ubiquitylation and degradation. (wikipedia.org)
  • HealthDay News) - Tyrosine kinase inhibitors (TKIs) appear to be safe in patients with chronic-phase (CP) chronic myeloid leukemia (CML) and chronic kidney disease (CKD) , according to a study published online in Cancer . (renalandurologynews.com)
  • To assess adherence and coping strategies in outpatients with chronic myeloid leukemia (CML) on oral tyrosine kinase inhibitors (TKIs). (ons.org)
  • 1997). The introduction of tyrosine kinase inhibitors (TKIs) in 2001 heralded the start of targeted therapies in hematopoietic cancers because of their distinct impact on tyrosine kinase, encoded by the CML-pathognomonic BCR-ABL gene (Kris et al. (ons.org)
  • Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML. (lu.se)
  • Tyrosine kinase inhibitors (TKIs) are frequently used in combined therapy to enhance treatment efficacy and overcome drug resistance. (muni.cz)
  • The results of a detailed analysis of cell signaling in the neuroblastoma cell lines revealed that TKIs inhibited the phosphorylation of the corresponding receptor tyrosine kinases, and thiosemicarbazones downregulated the expression of epidermal growth factor receptor, platelet-derived growth factor receptor, and insulin-like growth factor-1 receptor, leading to a strong induction of apoptosis. (muni.cz)
  • Tyrosine kinase inhibitors (TKIs), especially when combined with capecitabine, may improve the survival outcome of patients with HER2-positive (HER2+) breast cancer with brain metastases, according to the results of a meta-analysis presented at the 17th St. Gallen International Breast Cancer Conference 2021. (cancertherapyadvisor.com)
  • Drugs known as tyrosine kinase inhibitors, or TKIs, have revolutionized the treatment of chronic myelogenous leukemia (CML), a type of cancer in which the bone marrow produces too many semi-mature white blood cells. (dana-farber.org)
  • There are a variety of tyrosine kinase inhibitors (TKIs) that are used in oncology for the treatment of malignancies now and consequently there have been increased observations of tumour lysis syndrome (TLS) associated with these drugs. (touchoncology.com)
  • Tyrosine kinase inhibitors (TKIs) are small anticancer molecules targeting protooncogenic tyrosine kinase signalling pathways. (touchoncology.com)
  • 5 It is noteworthy that in high-risk patients with haematological malignancies, targeted therapy including TKIs, monoclonal antibodies, chimeric antigen receptors and proteasome inhibitors are often associated with TLS. (touchoncology.com)
  • Several tyrosine kinase inhibitors (TKIs) are emerging as new treatments for DTC, MTC and anaplastic TC (ATC), and can induce a clinical response and stabilize the disease. (unipi.it)
  • We evaluated the characteristics to progression such as clinical patterns of progression (dramatic, gradual, and local) with the prognosis of NSCLC patients treated with tyrosine kinase inhibitors (TKIs). (bvsalud.org)
  • A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. (wikipedia.org)
  • Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. (wikipedia.org)
  • The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphorylate serine or threonine residues and can discriminate between the kinase domains of the EGFR and that of the insulin receptor. (wikipedia.org)
  • It was further shown that in spite of the conservation of the tyrosine-kinase domains one can design and synthesize tyrphostins that discriminate between even closely related protein tyrosine kinases such as EGFR and its close relative HER2. (wikipedia.org)
  • Mediated by both on-target inhibition of BTK and variable off-target inhibition of other kinases including interleukin-2-inducible T-cell kinase (ITK), tyrosine-protein kinase (TEC), and endothelial growth factor receptor (EGFR), the toxicity profile of BTKis is closely linked to their pattern of kinase binding. (iasp-pain.org)
  • Reversible inhibitor of EGFR (HER1) and HER2 receptor kinases. (pharmacology2000.com)
  • Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. (currentmedicinalchemistry.com)
  • The receptor tyrosine kinases (RTK) are described in the following text. (ox.ac.uk)
  • Previous studies have implicated receptor tyrosine kinases in progesterone-induced [Ca2+]i signalling, and consequent induction of the acrosome reaction, in human spermatozoa. (dundee.ac.uk)
  • Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES. (bvsalud.org)
  • Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. (nih.gov)
  • Inhibition of Bruton's tyrosine kinase (BTK) has revolutionized the treatment landscape for patients with chronic lymphocytic leukemia (CLL). (iasp-pain.org)
  • and (b) direct inhibition of the slow Ca2+ channels (i.e. independent of inhibition of tyrosine kinase activity). (unboundmedicine.com)
  • Genetic mutation and pharmacological inhibition of Bruton's tyrosine kinase (Btk) both have been shown to prevent the development of collagen-induced arthritis (CIA) in mice, providing a rationale for the development of Btk inhibitors for treating rheumatoid arthritis (RA). (aspetjournals.org)
  • The inhibition caused by genistein was not affected by ciprofloxacin but was reproduced by a structurally dissimilar tyrosine kinase inhibitor, herbimycin A. (fluoridealert.org)
  • Prospective covalent docking allowed the identification of two lead series, resulting in a massive increase in inhibition of kinase activity and cell viability by irreversible inhibitors compared to the corresponding reversible scaffolds. (tu-darmstadt.de)
  • Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of quinazoline- and pyrido[3,4-d]pyrimidine-based analogues of the irreversible pan-erbB inhibitor, canertinib. (auckland.ac.nz)
  • By interfering with cell signalling pathways involved in cell proliferation, inhibition of EGFR-associated tyrosine kinase represents a novel approach to the treatment of solid tumours. (clinicaltrialsarena.com)
  • We have investigated the effects of tyrosine kinase inhibition on [Ca2+]i responses in large numbers of individual human spermatozoa. (dundee.ac.uk)
  • Previous reports of modulation of the progesterone-induced [Ca2+]i signal by tyrosine kinase inhibition probably reflect inhibition of the acrosome reaction. (dundee.ac.uk)
  • Do patient characteristics affect EGFR tyrosine kinase inhibitor treatment outcomes? (cdc.gov)
  • Survival of patients with chronic myeloid leukemia (CML) has improved significantly since the introduction of tyrosine kinase inhibitors (TKI) in 2001. (haematologica.org)
  • Managing toxicities of Bruton tyrosine kinase inhibitors. (iasp-pain.org)
  • Bruton Tyrosine Kinase (BTK) is a non receptor tyrosine kinase, and is one of the therapeutic targets for B-cell-driven malignancies. (currentmedicinalchemistry.com)
  • Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. (aai.org)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.com)
  • Etoposide (which inhibits topoisomerase II but has no effect on tyrosine kinase activity) also caused an increase in RINm5F cell death. (fluoridealert.org)
  • A 12-month, phase 2 trial, completed by Richeldi and colleagues, assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor nintedanib (formerly BIBF 1120) compared with placebo in patients with idiopathic pulmonary fibrosis. (medscape.com)
  • Bcr-Abl tyrosine-kinase inhibitor Protein kinase inhibitor Yaish P, Gazit A, Gilon C, Levitzki A (1988). (wikipedia.org)
  • Thank you for your request dated 20 January 2022 under the Official Information Act 1982 (OIA) for information relating to Pharmac approval of protein tyrosine kinase inhibitors. (pharmac.govt.nz)
  • a list of dates that protein tyrosine kinase inhibitors have been approved to be funded by PHARMAC. (pharmac.govt.nz)
  • Where found, I have included a hyperlink to the related decision notification for each listed protein tyrosine kinase inhibitor medicine. (pharmac.govt.nz)
  • Tarceva works by inhibiting receptor tyrosine kinase activity, the protein product of the EGFR gene. (clinicaltrialsarena.com)
  • Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase. (lu.se)
  • 5. Bixby D, Talpaz M. Mechanism of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. (sciendo.com)
  • Structural and mutational analyses indicate that the inhibitor binds both the active site and a nearby peripheral site unique to Lyp, thereby furnishing a solid foundation upon which inhibitors with therapeutic potency and selectivity can be developed. (elsevierpure.com)
  • Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. (lu.se)
  • PD168393 is a potent, selective and cell-permeable inhibitor of EGFR tyrosine kinase and ErbB2 . (medchemexpress.com)
  • Potent inhibitor of the complement Membrane Attack Complex (MAC) action. (lu.se)
  • The use of covalent irreversible binding inhibitors is an established concept for drug development. (tu-darmstadt.de)
  • Approved covalent BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib are associated with treatment limitations due to off-target side effects and the development of C481 substitution resistance mutations. (currentmedicinalchemistry.com)
  • Pirtobrutinib was approved by the US FDA on January 27, 2023, for the treatment of relapsed or refractory mantle cell lymphoma, including the resistance to covalent BTK inhibitors. (currentmedicinalchemistry.com)
  • Rilzabrutinib is an oral, reversible, covalent BTK inhibitor designed for immune-mediated diseases. (aai.org)
  • The present study analyzed the effects of three inhibitors, sunitinib, gefitinib, and lapatinib, combined with iron-chelating agents, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) or di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). (muni.cz)
  • The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy. (nih.gov)
  • Yu Y, Zhang J, Huang K, Lin Y, Song C. The efficacy and safety of tyrosine kinase inhibitors in HER-2 positive breast cancer with brain metastases: a systematic review and meta-analysis. (cancertherapyadvisor.com)
  • Here, we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy. (elsevierpure.com)
  • Evaluation of Treatment Efficacy of Tyrosine Kinase Inhibitors in Rare Single EGFR Exon 21 L861Q Mutation: Single Center Experience. (cdc.gov)
  • Dasatinib is a Src tyrosine kinase inhibitor that is effective both as a senolytic and as therapy for CML. (wikipedia.org)
  • IM, nilotinib, or dasatinib, with inhibitors of autophagy resulted in near complete elimination of phenotypically and functionally defined CML stem cells. (lu.se)
  • Treatment is with tyrosine kinase inhibitors (TKI) such as imatinib , dasatinib , nilotinib , bosutinib , and ponatinib , which significantly improve response and prolong survival. (msdmanuals.com)
  • It is a member of the Epidermal Growth Factor Receptor (EGFR) inhibitor class of agents and currently indicated for treatment of Non-Small Cell Lung Cancer (NSCLC) and pancreatic cancer. (clinicaltrialsarena.com)
  • Tarceva received US Food and Drug Administration (FDA) approval for the treatment of NSCLC in 2004 and gained the distinction of being the first EGFR inhibitor to show a survival benefit in lung cancer patients. (clinicaltrialsarena.com)
  • It is described as an angiogenesis inhibitor and a phytoestrogen . (wikipedia.org)
  • Mulitkinase inhibitor that targets several tyrosine kinase inhibitors implicated in tumor growth, pathologic angiogenesis, and metastatic progression. (medscape.com)
  • Imatinib mesylate (Gleevec), a 2-phenylaminopyridine that functions as a tyrosine kinase inhibitor, targets the c-kit domain expressed by some GISTs . (medscape.com)
  • Favorable π-π interactions between the 2-naphthyl moiety and a tyrosine side chain of the enzyme were observed for the thio analogues, which open up for the design of efficient GAG primers and inhibitors. (lu.se)
  • Herein, we report a virtual screening strategy that led to the discovery of irreversible inhibitors of FMS-like tyrosine kinase 3 (FLT3) involved in the pathogenesis of acute myeloid leukemia. (tu-darmstadt.de)
  • Optimum 4- and 6-substituents with known 7-substituents provided preferred irreversible inhibitors for pharmacodynamic testing in vivo. (auckland.ac.nz)
  • A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor Induction with Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults. (kucancercenter.org)
  • Effects of tyrosine kinase inhibitors on cell death induced by sodium fluoride and pertussis toxin in the pancreatic beta-cell line, RINm5F. (fluoridealert.org)
  • We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. (lu.se)
  • however, drug resistance to Gefitinib and other tyrosine kinase inhibitors presents a major issue. (oncotarget.com)
  • A virtual screening library was designed to target the highly conserved Cys828 residue preceding the DFG motif by modification of reported reversible inhibitors with chemically reactive groups. (tu-darmstadt.de)
  • Adavosertib is a Wee1 kinase inhibitor that is undergoing numerous clinical trials in the treatment of refractory solid tumors. (wikipedia.org)
  • The long-term toxicity profile of ibrutinib, a first-in-class inhibitor, is well characterized and includes a clinically significant incidence of cardiac arrhythmias, bleeding, infection, diarrhea, arthralgias, and hypertension. (iasp-pain.org)
  • Effects of genistein, a specific inhibitor of tyrosine kinase, on the L-type Ca2+ channels were examined in freshly isolated young (days 10-18) rat ventricular cells using the whole-cell patch-clamp technique. (unboundmedicine.com)
  • A genistein-sensitive tyrosine kinase does not appear to be involved in RINm5F cell survival under basal conditions. (fluoridealert.org)
  • Tyrosine kinase inhibitor treatment outcome in a single center cohort of chronic myeloid leukemia patients. (sciendo.com)
  • In the present study, tyrosine kinase inhibitors were used to investigate the mechanisms of action of NaF and pertussis toxin in the beta-cell line, RINm5F. (fluoridealert.org)
  • Together, our findings not only demonstrate that Btk plays an essential and conserved role in regulating immunoreceptor-mediated immune responses in both humans and rodents, but also provide evidence and mechanistic insights to support the development of selective Btk inhibitors as small-molecule disease-modifying drugs for RA and potentially other autoimmune diseases. (aspetjournals.org)
  • Usually, the discovery of new irreversible kinase inhibitors occurs serendipitously, showing that efficient rational approaches for the rapid discovery of new drugs are needed. (tu-darmstadt.de)
  • The lymphoid-specific tyrosine phosphatase (Lyp) has generated enormous interest because a single-nucleotide polymorphism in the gene (PTPN22) encoding Lyp produces a gain-of-function mutant phosphatase that is associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus. (elsevierpure.com)
  • Survival outcomes of east Asian patients with advanced non-small cell lung cancer treated with first-line EGFR tyrosine kinase inhibitors: A network meta-analysis of real-world evidence. (cdc.gov)
  • The bcr-abl oncoprotein has uncontrolled tyrosine kinase activity, which deregulates cellular proliferation, decreases adherence of leukemia cells to the bone marrow stroma, and protects leukemic cells from normal programmed cell death (apoptosis). (msdmanuals.com)
  • The activity of this pathway is most evident in cells exposed to pro-apoptotic stimuli where the effects of pertussis toxin can be blocked by inhibitors of tyrosine kinase enzymes. (fluoridealert.org)