• inhibit
  • Analysis of proteins that regulate cell cycle arrest suggested that both drugs inhibit the checkpoint kinases Chk1 and/or Chk2. (aacrjournals.org)
  • Angoline and chelerythrine, benzophenanthridine alkaloids that do not inhibit protein kinase C. (abcam.com)
  • The present invention relates to novel compounds selected from 2-aminoaryloxazoles that selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic and degenerative disorders. (google.com)
  • Compounds have been developed to selectively inhibit the tyrosine kinase. (wikipedia.org)
  • Due to increasing resistance and intolerance to imatinib efforts were made to develop new drugs that could inhibit the Bcr-Abl tyrosine kinase. (wikipedia.org)
  • specifically, the C2 domain of PKCε at amino acids 14-21 (also known as εV1-2) binds RACK2, and peptide inhibitors targeting εV1-2 inhibit PKCε translocation and function in cardiomyocytes, while peptide agonists augment translocation. (wikipedia.org)
  • This theory arose from the observation that PKMζ perfused post synaptically into neurons causes synaptic potentiation, and selective inhibitors of PKMζ like zeta inhibitory peptide (ZIP), when bath applied one hour after tetanization, inhibit the late phase or maintenance of LTP. (wikipedia.org)
  • catalytic
  • The identification of the enzyme(s) involved in the formation of N- desmethyl LY333531 was then accomplished by correlating the rate of formation of the metabolite with immunoquantified levels and/or the associated form-selective catalytic activities for the drug-metabolizing enzymes by a bank of human liver microsomes. (aspetjournals.org)
  • Janus
  • The nonreceptor tyrosine kinases Janus kinase (Jak)1 and Jak3, constitutively associated with IL-4Rα and γc, respectively ( 6 )( 7 )( 8 ), become activated after IL-4 binding to its receptor and phosphorylate some or all of the conserved tyrosines of IL-4Rα. (rupress.org)
  • Apoptosis
  • P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. (wikipedia.org)
  • This kinase has been shown to be involved in many different cellular functions, such as apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. (wikipedia.org)
  • modulates
  • In cardiac muscle cells, PKCε regulates muscle contraction through its actions at sarcomeric proteins, and PKCε modulates cardiac cell metabolism through its actions at mitochondria. (wikipedia.org)
  • binds
  • Unfortunately, UCN-01 binds avidly to human plasma proteins, limiting bioavailability. (aacrjournals.org)
  • 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)
  • bisindolylmaleimide
  • As a probable mechanism, we found that sDPP-4 caused dose-dependent increases in the expression levels of toll-like receptor 4 (TLR4) and TLR2 in RAW264.7 cells, and that these alterations were inhibited by vildagliptin, M6P, or bisindolylmaleimide II, a protein kinase C inhibitor. (gopubmed.org)
  • atypical
  • Thus, conventional and novel PKCs are activated through the same signal transduction pathway as phospholipase C. On the other hand, atypical (a)PKCs (including protein kinase Mζ and ι / λ isoforms) require neither Ca2+ nor diacylglycerol for activation. (wikipedia.org)
  • activity
  • The only significant correlation observed was with the form-selective activity for CYP3A. (aspetjournals.org)
  • Hypoxic ventilatory response is modulated by protein kinase C (PKC) activity within the nucleus tractus solitarius (NTS) of the conscious rat. (springer.com)
  • PIN polarity is regulated by the AGC protein kinase, PINOID (PID), while ABCB activity was shown to be dependent on interaction with the FKBP42, TWISTED DWARF1 (TWD1). (embopress.org)
  • Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia. (nih.gov)
  • 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)
  • In addition to their estrogenic activity, various TPE derivatives like tamoxifen and clomifene have been found to act as protein kinase C inhibitors. (wikipedia.org)
  • encodes
  • Bcr-Abl was regarded as highly attractive target for drug intervention since the Bcr-Abl fusion gene encodes a constitutively activated kinase. (wikipedia.org)
  • Human PRKCE gene (Ensembl ID: ENSG00000171132) encodes the protein PKCε (Uniprot ID: Q02156), which is 737 amino acids in length with a molecular weight of 83.7 kDa. (wikipedia.org)
  • mRNA
  • The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats. (gopubmed.org)
  • Treatment with a protein kinase C inhibitor partially decreased losartan-mediated RGS2 mRNA expression. (gopubmed.org)
  • In contrast, there was a profound and time-dependent increase in endothelial prepro-ET-1 mRNA and intravascular ET-1 abundance (by ELISA) as well as in smooth muscle endothelin B receptor mRNA and functional protein (by superfusion bioassay) on raising the perfusion pressure from 5 to 20 mm Hg, but not from 0 to 5 mm Hg, for up to 12 hours. (ahajournals.org)
  • signal
  • SU6656 has been used primarily as a research tool to investigate the function of Src family kinases in cellular signal transduction processes and biology. (wikipedia.org)
  • Role
  • In vivo evidence for a role of protein kinase C in peripheral nociceptive processing. (apexbt.com)
  • Although the role of IRS-2 and other PTB domain proteins during Th2 cell differentiation is unclear, Stat6 plays a critical role in driving this process ( 22 )( 23 )( 24 )( 25 ). (rupress.org)
  • In the development of imatinib, the structure of Bcr-Abl tyrosine kinase played a limited role because it was unknown. (wikipedia.org)
  • sought
  • P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes, e.g. pamapimod. (wikipedia.org)
  • activation
  • Over the last several years, evidence has accumulated that implicates the hyperglycemia-induced activation of protein kinase C (PKC 1 ) as one of the mechanisms responsible for the development and/or progression of chronic complications of diabetes. (aspetjournals.org)
  • Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. (springer.com)
  • Gozal, D., and E. Gozal E. Hypoxic ventilatory roll-off is associated with decreases in protein kinase C activation within the nucleus tractus solitarius of the rat. (springer.com)
  • New forms of resistance can arise as: missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or the constitutive activation of downstream signaling molecules such as Src-family kinases. (wikipedia.org)
  • 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)
  • ROS generated via pharmacologic activation of the mitochondrial potassium-sensitive ATP channel (mitoK(ATP)) and the endogenous G-protein coupled receptor ligand, apelin. (wikipedia.org)
  • nucleus
  • The protein also seems to be involved, through the nucleus accumbens, in the consolidation and reconsolidation of the memory related to drug addiction. (wikipedia.org)
  • cellular
  • Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), Ultraviolet light, and growth factors. (wikipedia.org)
  • discovery
  • Drug discovery that specifically targeted the ATP binding site of a single kinase was regarded as quite a challenging task since hundreds of protein kinases were known in the human genome. (wikipedia.org)
  • In 2009 the Sebti lab discovered a new proteasome inhibitor called PI-083 Prescient Therapeutics originated in 2014 from two drug discovery programmes pioneered by the Sebti lab, PTX-200 and PTX-100. (wikipedia.org)
  • cells
  • However, Gö6976 potently abrogated S and G 2 arrest and enhanced the cytotoxicity of the topoisomerase I inhibitor SN38 only in p53-defective cells. (aacrjournals.org)
  • Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells. (nih.gov)
  • Biology
  • 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)
  • known
  • 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)