• inhibits
  • We have now found that treatment of bag cell neurons with the protein kinase inhibitor 1-[5- isoquinolinesulfonyl]-2-methyl piperazine (H-7) inhibits the phorbol ester-induced enhancement of bag cell action potentials and prevents the enhancement of calcium current by phorbol esters. (jneurosci.org)
  • Sunitinib also inhibits CD117 (c-KIT), the receptor tyrosine kinase that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors. (wikipedia.org)
  • PDGFR
  • Sugen went public in October 1994 (NASDAQ: SUGN), and shortly after filed its first Investigational New Drug (IND) application, for a PDGFR inhibitor, SU101. (wikipedia.org)
  • This failed clinically, but was followed by a different series of compounds that inhibited VEGFR kinases (involved in angiogenesis) as well as PDGFR and Kit. (wikipedia.org)
  • 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)
  • Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. (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)
  • crizotinib
  • Previously, it was only indicated for patients who had developed resistant to crizotinib, another ALK-positive inhibitor, but has since had its usage expanded to serve as a primary option for metastatic NSCLC. (wikipedia.org)
  • Work started at Sugen also contributed to the development of the ALK inhibitor crizotinib (Xalkori), FDA-approved for NSCLC in 2011. (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)
  • amino acids
  • There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues. (wikipedia.org)
  • 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)
  • development
  • Alternative strategies, such as targeting other kinases in the cascade or development of allosteric inhibitors have been proposed. (bmj.com)
  • Several years later, Novartis Pharmaceuticals Corporation, began working towards development of targeted ALK inhibitors. (wikipedia.org)
  • As a result, most of inhibitor development efforts has also been towards PIM1. (wikipedia.org)
  • The concept of inhibiting kinases by small molecules that mimicked the ATP structure was generally thought to be infeasible when the company was founded (due to the high (mM) concentration of ATP in cells), and Sugen has been credited with pioneering this area, leading to protein kinases being the second most active area of drug development, largely based on ATP-competitive inhibitors. (wikipedia.org)
  • Conversely, Sugen was an investor in and collaborator with Selectide for the development of peptide kinase inhibitors. (wikipedia.org)
  • proliferation
  • 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)
  • cytokine
  • The mitogen activated protein (MAP) kinases are especially attractive because they regulate both cytokine production and cytokine action. (bmj.com)
  • 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)
  • activity
  • 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)
  • 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)
  • biology
  • Sugen also generated extensive basic research on kinase biology, including the publication of almost 300 research papers, the definition of the human kinome, and the discovery of over 140 human kinase genes. (wikipedia.org)
  • structures
  • 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)
  • oncogene
  • The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). (clinicaltrials.gov)
  • 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)
  • compound
  • We have previously identified the compound cambinol, an inhibitor of the human sirtuins SIRT1 and SIRT2, which is selectively toxic to Burkitt's lymphoma cells. (washington.edu)
  • Other programs also transferred to Pfizer, including a follow-on compound to SU11248, known as SU14813, and programs on Met and PAK kinases. (wikipedia.org)
  • cancer
  • In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. (hindawi.com)
  • AZD6244 ( ARRY-142886 ) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. (clinicaltrials.gov)
  • 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)
  • While PIM kinase to autophosphorylate, the functional consequences are not known. (wikipedia.org)