• targets
  • We have synthesized analogues of these compounds, identifying more selective sirtuin inhibitors and more potent calmodulin-dependent protein kinase inhibitors.The sirtuins are a family of NAD+-dependent deacetylases that regulate cellular aging and gene silencing in simple organisms and appear to play important regulatory roles in human cells that make them attractive anti-cancer targets. (washington.edu)
  • compounds
  • 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)
  • extracellular
  • The proliferative effects of ROCK on vascular endothelial cells is due to the activation of extracellular signal-regulated kinase (ERK). (wikipedia.org)
  • enzymes
  • Safingol competitively competes with phorbol dibutyrate at regulatory domains of the protein kinase C family, inhibiting the activation of such enzymes as PKCβ-I, PKCδ, and PKCε. (wikipedia.org)
  • analogues
  • In an effort to identify additional CaMK inhibitors that exhibit more potent activity in triggering leukemia cell differentiation, we synthesized 45 analogues of KN-62 and determined their ability to induce HL-60 cell differentiation. (washington.edu)
  • blockade
  • ii) the oncogenic switch to another pathway that rescues cancer cells from kinase blockade. (unina.it)
  • Although the available data suggest a rationale for MAP kinase blockade, development of drugs has been hampered by toxicity and limited efficacy. (bmj.com)
  • tumor
  • Participants will be screened with a medical history, physical examination, blood tests, imaging studies, and potentially, tumor biopsy tests to determine whether a participant's NSCLC contains mutations in the KRAS protein. (clinicaltrials.gov)
  • Several function as tumor suppressor proteins. (wikipedia.org)
  • high affinity
  • 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)
  • CYP3A4
  • It is a substrate for CYP3A4 and hence grapefruit juice and other CYP3A4 inhibitors will increase its action and inducers like St. John's wort will decrease it. (wikipedia.org)
  • structural
  • Structural analysis of kinase pockets demonstrated that main chain atoms which are conserved in their relative positions to staurosporine contributes to staurosporine promiscuity. (wikipedia.org)
  • Thus far, most of the structural information pertaining to the PIM kinase family has been limited to PIM1. (wikipedia.org)
  • treatment
  • Kinase inhibitors such as dasatinib are often used in the treatment of cancer and inflammation. (wikipedia.org)
  • ii) thyroid cancer cells escape treatment with vemurafenib by switching to another signaling pathway and that inhibitors of the IGF1R/PI3K/AKT signaling cascade may be exploited to overcome resistance of thyroid cancer cells lines to BRAF PKI. (unina.it)
  • These approaches might permit effective use of MAP kinase inhibitors for the treatment of rheumatic and immune-mediated diseases. (bmj.com)
  • Mubritinib (TAK-165) is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer. (wikipedia.org)
  • Ceritinib is an aplastic lymphoma kinase (ALK)-positive inhibitor primarily used for the treatment of metastatic NSCLC. (wikipedia.org)
  • Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells. (wikipedia.org)
  • In June 2006, a phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib, another tyrosine kinase inhibitor currently used as a first-line treatment. (wikipedia.org)
  • amino acids
  • The gene splicing converted a protein with 70 amino acids into one of 109 amino acids, and did not change the inhibitory potency to PKA, but changed it from a protein that had no detectable PKG inhibitory activity to one that now inhibited PKG in the nanomolar range. (biochemj.org)
  • oncogenic
  • Thyroid cancer is frequently associated to the oncogenic conversion of protein kinases such as RET (medullary thyroid cancer) and BRAF (papillary and undifferentiated thyroid cancer). (unina.it)
  • activate
  • Currently there are several drugs launched or in development that target protein kinases and the receptors that activate them: Note: AD = Approval date. (wikipedia.org)
  • Cytokines including interleukins, interferons and hemopoietins activate the Janus kinases, which associate with their cognate receptors. (wikipedia.org)
  • It was found to reduce ATP levels, activate 5'-AMP-activated protein kinase and affect mitochondrial production of reactive oxygen species (ROS). (wikipedia.org)
  • cytokine
  • The mitogen activated protein (MAP) kinases are especially attractive because they regulate both cytokine production and cytokine action. (bmj.com)
  • Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. (wikipedia.org)
  • enhances
  • SIRT2 appears to be the relevant target for cambinol-induced Daudi cell toxicity.KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances the terminal differentiation of retinoic acid sensitive human myeloid leukemia cell lines. (washington.edu)
  • Exposure of the bag cell neurons of Aplysia to activators of protein kinase C, such as phorbol esters, enhances electrically evoked action potentials by increasing the voltage-dependent calcium current. (jneurosci.org)
  • regulation
  • RKIP is a member of the phosphatidylethanolamine-binding protein family and has displayed disruptive regulation on the Raf-1-MEK1/2, ERK1/2 and NF-kappaB signalling pathways, by interaction with the Raf-1 kinase. (wikipedia.org)
  • potency
  • The SAR suggests that the addition of potential hydrogen bonding groups at the R1 and R2 positions dramatically increases potency against both kinases. (wikipedia.org)
  • molecular
  • 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)
  • cell
  • We have found that microinjection of a protein inhibitor of cAMP-PK (PKA-I) into isolated bag cell neurons prevents and reverses the effect of the adenylate cyclase activator forskolin on action potentials of these cells. (jneurosci.org)
  • Cell cycle progression is negatively controlled by cyclin-dependent kinases inhibitors (called CDIs, CKIs or CDKIs). (wikipedia.org)
  • Safingol is also a putative inhibitor of sphingosine kinase 1 (SphK), which catalyzes the production of sphingosine 1-phosphate (S1P), an important mediator of cancer cell growth, proliferation, invasion, and angiogenesis. (wikipedia.org)
  • activation
  • We have hypothesized that this effect is mediated by the activation of protein kinase C (PKC). (jneurosci.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)
  • Typically, kinases' active state is characterized by the presence of the conserved lysine, a closed lobe conformation, and a well-structured activation segment. (wikipedia.org)
  • The crystal structures show that the unphosphorylated activation segment forms many polar interactions with the lower kinase lobe, which stabilizes the active conformation. (wikipedia.org)
  • family
  • The mammalian JAK family has four members: JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). (wikipedia.org)
  • 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)