ARTICLE Received 27 Dec 2014 | Accepted 3 Jul 2015 | Published 12 Aug 2015 DOI: 10.1038/ncomms8999 OPEN Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells Fabrizio Capuani1,w,*, Alexia Conte1,*, Elisabetta Argenzio1,w, Luca ...
Jia et al. conducted counter-screening of active compounds against WT-EGFR and discovered the first non-ATP-competitive allosteric EGFR L858R/T790M/C797S inhibitor based on the thiazolamide scaffold (EAI001,2) [96]. The X-ray crystal structure of EAI001 (2) in complex with EGFR T790M shows...
When K721 mono-methylation occurs, this distance is predicted to range from 2.19 to 4.79 Angstrom. In the context of this variability, K721 mono-methylation is expected to allow erlotinib to bind to the ATP-binding pocket without any van der Waals clash. This though pre- supposes that the...
Jia et al. conducted counter-screening of active compounds against WT-EGFR and discovered the first non-ATP-competitive allosteric EGFR L858R/T790M/C797S inhibitor based on the thiazolamide scaffold (EAI001,2) [96]. The X-ray crystal structure of EAI001 (2) in complex with EGFR T790M shows...
Overexpression or upregulated activity of EGFR is an important molecular characteristic that has been noted in numerous epithelial solid tumors such as colorectal cancer (CRC), non-small cell lung cancer (NSCLC), HNC, pancreatic cancer, breast cancer, and brain cancer. However, distinguishable mechan...
Accordingly, compounds that have a hydrazine-1-carbothioamide moiety showed good activity, compared with those containing a hydrazine-1-carboxamide moiety (IC50 range = 8.59–23.13 µM, compared with 8.56–27.83 µM), respectively. According to the terminal hydrophobic moiety, compounds 3A, 3B,...
In normal cells, the expression of EGFR is estimated at between 40,000 and 100,000 receptors per cell;7 however, in cancer cells, the overexpression of more than 106 receptors per cell has been observed.8 The activation of EGFR requires ligand binding. The binding of the EGF ligand to ...
NSCLC: non-small cell lung cancer PCR: polymerase chain reaction PARP: polyADP-ribose polymerase PR: progesterone receptor SPKANKEI: amino acids Serine-Proline-Lysine-Alanine-Asparagine-Lysine-Glutamic acid-Isoleucine TKIs: tyrosine kinase inhibitors.References...
PET imaging with 89Zr-IgG [230– 250 μCi (8.51–9.25- MBq, 306–336 pmol, 46–50 μg) was conducted in mice with BxPC-3 and AsPC-1 tumors to assess non-specific accumulation of the tracer. Tissue distribution and in vivo competitive specificity. The tissue distribution of ...
HDAC1 is the prototypical human histone deacetylase (HDAC) enzyme responsible for catalyzing the removal of acetyl group from lysine residues on many substrate proteins. By deacetylating histones and non-histone proteins, HDAC1 has a profound effect on t