• potent
  • Peroxovanadate (PVN), a potent protein tyrosine phosphatase inhibitor, had no effect on the basal Ca 2+ current. (aspetjournals.org)
  • SMARCB1 is a core protein subunit of the 15 subunit SWI/SNF (or BAF) complex involved in regulating the nucleosome architecture of our genome and has been shown to be a potent tumor suppressor gene, meaning that its primary role is to control cell division and to even halt division under appropriate circumstances (i.e. signals to over-replicate). (wikipedia.org)
  • selective
  • Subsequent studies have confirmed that SU6656 is relatively selective for Src family kinases but some additional biochemical activities have been identified including: BRSK2, AMPK, Aurora C, Aurora B, CaMKKβ. (wikipedia.org)
  • gene
  • ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ETV6 (previously known as TEL) gene. (wikipedia.org)
  • Two unrelated kindreds were found to have autosomal dominant inherited mutations in the ETV6 gene, one family with a germline DNA substitution termed L349P that lead to replacing leucine with proline at amino acid 349 in the DNA binding domain of the ETV6, the second, termed N385fs, in germline DNA caused the lose of five base pairs ETV6 and a truncated ETV6 protein. (wikipedia.org)
  • Bcr-Abl was regarded as highly attractive target for drug intervention since the Bcr-Abl fusion gene encodes a constitutively activated kinase. (wikipedia.org)
  • This gene encodes a member of the tyrosine kinase and, to be more specific, the Janus kinases (JAKs) protein families. (wikipedia.org)
  • A mutation in this gene has been associated with hyperimmunoglobulin E syndrome (HIES) - a primary immunodeficiency characterized by elevated serum immunoglobulin E. Tyrosine kinase 2 has been shown to interact with FYN, PTPN6, IFNAR1, Ku80 and GNB2L1. (wikipedia.org)
  • Initially
  • SU6656 was initially identified as a Src kinase inhibitor by virtue of its ability to reverse an effect that an activated mutant form of Src (hu SRC Y530F) has on the actin cytoskeleton, namely the formation of podosome rosettes, otherwise known as invadopodia. (wikipedia.org)
  • cells
  • Here, we demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary CD34 + human AML blast progenitor cells (BPC) expressing FLT3-ITD. (aacrjournals.org)
  • Furthermore, cotreatment with JQ1 and the pan-histone deacetylase inhibitor (HDI) panobinostat synergistically induced apoptosis of FLT3-TKI-resistant MOLM13-TKIR and MV4-11-TKIR cells. (aacrjournals.org)
  • Cells were harvested 18 h after transfection and lysed at 4 C in a Dounce homogenizer in 250 mm sucrose, 20 mm TrisHCl, 1 mm CaCl2, 1 mm MgCl2, cOmplete protease inhibitor cocktail (Roche Applied Science), pH 8. (molecularcircuit.com)
  • Vascular inflammation can be caused by upregulation of Ang-II, which is produced locally by inflamed vessels and induces synthesis and secretion of IL-6, a cytokine responsible for induction of angiotensinogen synthesis in liver through JAK/STAT3 pathway, which gets activated through high affinity membrane protein receptors on target cells, termed IL-6R-chain recruiting gp-130 that is associated with tyrosine kinases (Jaks 1/2, and Tyk2 kinase). (wikipedia.org)
  • drug
  • While drug screening was used to develop imatinib, second generation TKI's were developed with rational drug design approach due to increased knowledge in structural biology of the Bcr-Abl tyrosine kinase. (wikipedia.org)
  • Imatinib (Gleevec) was discovered in 1992 and is regarded as first generation drug since it is the first Bcr-Abl tyrosine kinase inhibitor to be used in the treatment of CML. (wikipedia.org)
  • Sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar), is a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (hepatocellular carcinoma), and radioactive iodine resistant advanced thyroid carcinoma. (wikipedia.org)
  • activity
  • Although several Src-family inhibitors are available, the development of Lyn-specific inhibitors, or inhibitors with reduced off-target activity to Lyn, has been hampered by the lack of structural data on the Lyn kinase. (edu.au)
  • With a replacement of the imidazole group with a benzamido group, the compound's specificity increased while its activity as a kinase inhibitor remained the same. (wikipedia.org)
  • activate
  • Cytokines including interleukins, interferons and hemopoietins activate the Janus kinases, which associate with their cognate receptors. (wikipedia.org)
  • Resistance
  • Even though the first Bcr-Abl TK inhibitor was named "the magic bullet" to cure cancer by TIME magazine, a second generation of Bcr-Abl TKI was subsequently developed to combat the initial resistance that emerged. (wikipedia.org)
  • active
  • Recently, ponatinib was shown to be active against AC220-resistant kinase domain mutants of AML-expressing FLT3-ITD ( 6 , 11 ). (aacrjournals.org)
  • The Lyn kinase domain was determined in its "active" conformation, but in the unphospho-rylated state. (edu.au)
  • The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. (wikipedia.org)
  • activation
  • The shift of the AspPheGly triad at the N-terminal end of the activation loop results in the exposure of a binding pocket which can be utilized by inhibitors. (wikipedia.org)
  • Signalling through IL-4/IL-13 complexes is thought to occur through IL-4Rα-chain, which is responsible for activation of JAK-1 and Tyk2 kinases. (wikipedia.org)
  • domain
  • Since then crystallographic studies have revealed that imatinib binds to the kinase domain of Abl only when the domain adopts the inactive or "closed" conformation. (wikipedia.org)
  • form
  • Analysis of gB Multimerization and Competition Dialysis gB multimerization was induced by mixing purified gB or gBC777A, obtained in their spontaneous 600-kDa form, with 50 m cholesterol dissolved into the protein buffer for 1 h at 37 C, without Exemestane supplier further manipulations. (molecularcircuit.com)