• 2017
  • As of 2017[update], Read's research interests are in protein crystallography and maximum likelihood estimation. (wikipedia.org)
  • compounds
  • To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. (springer.com)
  • Among a large series of compounds built around a benzo[c]-[2,aphthyridine-8-carboxylic acid scaffold, CX-4945 was chosen for its high potency and selectivity as an inhibitor of CK2. (wikipedia.org)
  • 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)
  • BIM-1 and the related compounds BIM-2, BIM-3, and BIM-8 are bisindolylmaleimide-based protein kinase C (PKC) inhibitors. (wikipedia.org)
  • regulates
  • mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. (wikipedia.org)
  • protease inhibitors
  • Darnag R, Minaoui B, Fakir M (2012) QSAR models for prediction study of HIV protease inhibitors using support vector machines, neural networks and multiple linear regression. (springer.com)
  • constitutively active
  • This abnormality was discovered by Peter Nowell in 1960 and is a consequence of fusion between the Abelson (Abl) tyrosine kinase gene at chromosome 9 and the break point cluster (Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML. (wikipedia.org)
  • mTOR
  • The most established mTOR inhibitors are so-called rapalogs (rapamycin and its analogs), which have shown tumor responses in clinical trials against various tumor types. (wikipedia.org)
  • The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its inhibitor, rapamycin. (wikipedia.org)
  • Several downstream pathways that regulate cell-cycle progression, translation, initiation, transcriptional stress responses, protein stability, and survival of cells are signaling through mTOR. (wikipedia.org)
  • Many human tumors occur because of dysregulation of mTOR signaling, and can confer higher susceptibility to inhibitors of mTOR. (wikipedia.org)
  • Therefore, mTOR is an interesting therapeutic target for treating multiple cancers, both the mTOR inhibitors themselves or in combination with inhibitors of other pathways. (wikipedia.org)
  • Activated Akt can then go on to activate or deactivate its myriad substrates (e.g. mTOR) via its kinase activity. (wikipedia.org)
  • staurosporine
  • This staurosporine analog is a highly potent cell permeable inhibitor of CaM kinase and phosphorylase kinase (IC50 = 1.8 and 1.7 nmol/L, respectively). (wikipedia.org)
  • The value of such calculations lies in understanding a variant was designed which showed improved binding characteristics of configurationally stable atropisomeric bisindolylmaleimides where the two kinase domains, and two different inhibitor conformers bind in different orientations, the hinge region of staurosporine-Pim-1 resembles co-crystallized as an asymmetric pair of biosynthetically 'related' indolocarbazole analogs. (wikipedia.org)
  • subunit
  • The FAT domain consists of repeats, referred to as HEAT (Huntingtin, Elongation factor 3, A subunit of protein phosphatase 2A and TOR1). (wikipedia.org)
  • The Gs alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex. (wikipedia.org)
  • binds
  • 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)
  • activity
  • Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity. (uniprot.org)
  • Bozorgi AH, Bagheri M, Aslebagh R, Rajabi MS (2013) A structure-activity relationship survey of histone deacetylase (HDAC) inhibitors. (springer.com)
  • Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase, thereby inhibiting glucose oxidation via pyruvate dehydrogenase. (ox.ac.uk)
  • CX-4945 was originated by now-defunct Cylene Pharmaceuticals of San Diego, California, as the culmination of a lengthy process of rational, structure-based molecular modification of a lead compound known to have PARP inhibitor activity. (wikipedia.org)
  • 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)
  • The close relationship of DMPK to the Rho-kinases has led to speculation whether DMPK activity may be regulated in vivo by small G proteins, particularly of the Rho family. (wikipedia.org)
  • In this model, transient activation of kinase activity would occur in response to G protein second messengers, while longterm activation of DMPK could be mediated by a membrane associated protease that cleaves DMPK-1 to release cytosolic DMPK-2 in a persistently activated form. (wikipedia.org)
  • novel
  • Novel bradykinin signaling in adult rat cardiac myocytes through activation of p21-activated kinase. (biomedsearch.com)
  • Balanol was discovered in 1993 in the search for novel inhibitors of PKC, a member of a family of serine/threonine kinases whose overactivation is associated with numerous human diseases of signal transduction including cancer. (wikipedia.org)
  • Subsequently, Cantley and colleagues demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the novel phosphoinositide PtdIns(3,4,5)P3 previously identified in neutrophils The phosphoinositol-3-kinase family is divided into four different classes: Class I, Class II, Class III, and Class IV. (wikipedia.org)
  • superfamily
  • The TGF beta superfamily of ligands include: Bone morphogenetic proteins (BMPs), Growth and differentiation factors (GDFs), Anti-müllerian hormone (AMH), Activin, Nodal and TGFβ's. (wikipedia.org)
  • signaling molecules
  • 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)
  • 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)