Recent submissions
Now showing items 461-480 of 658
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canSAR: updated cancer research and drug discovery knowledgebase.
(OXFORD UNIV PRESS, 2014-01-01)canSAR (http://cansar.icr.ac.uk) is a public integrative cancer-focused knowledgebase for the support of cancer translational research and drug discovery. Through the integration of biological, pharmacological, chemical, ... -
Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53-dependent mechanism
(Springer Science and Business Media LLC, 2016-02-01)The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation ... -
DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes
(2016-01-01)Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and ... -
Integrated multiomics approach identifies calcium and integrin-binding protein-2 as a novel gene for pulse wave velocity
(Ovid Technologies (Wolters Kluwer Health), 2016-01-01)Background: Carotid-femoral pulse wave velocity (PWV) is an important measure of arterial stiffness, which is an independent predictor of cardiovascular morbidity and mortality. In this study, we used an integrated genetic, ... -
ChEMBL: a large-scale bioactivity database for drug discovery.
(OXFORD UNIV PRESS, 2012-01-01)ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published literature on a regular ... -
canSAR: an integrated cancer public translational research and drug discovery resource.
(OXFORD UNIV PRESS, 2012-01-01)canSAR is a fully integrated cancer research and drug discovery resource developed to utilize the growing publicly available biological annotation, chemical screening, RNA interference screening, expression, amplification ... -
Crystal structure of an Aurora-A mutant that mimics Aurora-B bound to MLN8054: insights into selectivity and drug design
(2010-01-01)The production of selective protein kinase inhibitors is often frustrated by the similarity of the enzyme active sites. For this reason, it is challenging to design inhibitors that discriminate between the three Aurora ... -
A Phase 1, open-label, multicentre study to compare the capsule and tablet formulations of AZD5363 and explore the effect of food on the pharmacokinetic exposure, safety and tolerability of AZD5363 in patients with advanced solid malignancies: OAK.
(SPRINGER, 2018-05-01)PURPOSE: AZD5363 is a potent pan-AKT inhibitor originally formulated as a capsule; a tablet was developed for patient convenience and manufacturing ease. This study assessed the PK comparability of both formulations (Part A) ... -
Focal Adhesion Kinase (FAK) tyrosine 397E mutation restores the vascular leakage defect in endothelium‐specific FAK‐kinase dead mice
(Wiley, 2017-07-01)<jats:title>Abstract</jats:title><jats:p>Focal adhesion kinase (<jats:styled-content style="fixed-case">FAK</jats:styled-content>) inhibitors have been developed as potential anticancer agents and are undergoing clinical ... -
Loss of MMP-8 in ductal carcinoma in situ ( DCIS)-associated myoepithelial cells contributes to tumour promotion through altered adhesive and proteolytic function
(2017-01-01)Background: Normal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix ... -
The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology.
(UPV/EHU Press, 2011-01-01)The EGFR/Erb-B receptor tyrosine kinases each play distinct and complementary roles in normal breast development. The four receptors form both homodimers and heterodimers in response to binding by ligands which show ... -
Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
(2018-01-01)Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites ... -
Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells
(Springer Science and Business Media LLC, 2002-04-01)Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells. We previously reported that the FrbB2 oncoprotein prolongs and amplifies growth factor ... -
Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.
(NATURE PUBLISHING GROUP, 2015-01-02)The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ... -
CNS cancer immunity cycle and strategies to target this for glioblastoma.
(Impact Journals, LLC, 2018-04-27)Immunotherapeutics have revolutionized the management of solid malignancies over the last few years. Nevertheless, despite relative successes of checkpoint inhibitors in numerous solid tumour types, success in tumours of ... -
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
(NATURE PORTFOLIO, 2018-01-23)There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples ... -
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
(IMPACT JOURNALS LLC, 2013-08-25)The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ... -
Synthesis and profiling of a 3-aminopyridin-2-one-based kinase targeted fragment library: Identification of 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one scaffold for monopolar spindle 1 (MPS1) and Aurora kinases inhibition.
(PERGAMON-ELSEVIER SCIENCE LTD, 2018-07-15)Screening a 3-aminopyridin-2-one based fragment library against a 26-kinase panel representative of the human kinome identified 3-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2(1H)-one (2) and 3-amino-5-(pyridin-4-yl)pyridi ... -
HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target.
(AMER ASSOC CANCER RESEARCH, 2018-05-15)Purpose: Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) ...