Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based...
We report here that imatinib inhibits SARS-CoV-2 infection and Spike-mediated cell–cell membrane fusion in Abl-kinases knockout cells suggesting an imatinib off-target effect. Furthermore, we show that imatinib did not impair hACE2-Spike-interaction but rather stabilized Spike protein and changed...
of non-specific agents probably inhibit viral replication due to their physicochemical (lysosomotropic) properties leading to a perturbation of acidic organelles rather than due to their specific mode of action (such as blockade of histamine or sigma receptors or the inhibition of tyrosine kinases). ...
The abnormal phosphorylation of tau leads to the formation of NFTs produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia. Hence, tau kinases have become potential drug target candidates for small molecule inhibitors. With an aim to explore the...
Methods have also been developed that rapidly assess compound activity against specific activation states of kinases. There has also been a development of newer methods that move beyond traditional biochemical formats, which take a 'whole cell' approach to compound profiling. Areas Covered: This ...
These data indicate that TKIs, through off-target inhibition of kinases important in B-cell signaling, reduce memory B-cell frequencies and induce significant impairment of B-cell responses in CML.Blood
P90 ribosomal S6 kinases (RSK) are ubiquitously expressed and regulate responses to neurohumoral stimulation. To study the role of RSK signalling on cardiac myocyte function and protein phosphorylation, pharmacological RSK inhibitors were tested. Here, the ATP competitive N-terminal kinase domain-...
The highest number of predicted interactions were for drugs targeting G protein-coupled receptors (GPCRs), enzymes, and kinases with 10,648, 4081, and 3678 interactions, respectively. Notably, 17,283 (63%) of the off-target interactions have been confirmed in vitro. Approxima...
exogenous siRNAs are thought to be dependent on phosphorylation by kinases following intracellular uptake30,31. To characterize the relationship of RISC loading to the hepatotoxicity observed with a random subset of modified GalNAc-siRNAs (Supplementary Fig.1)8in rodent toxicity studies, the 5′-end ...
De Franceschi, L.. Deficiency of Src family kinases Fgr and Hck results in activation of erythrocyte K/Clcotransport., 220–227 (1997). PubMed CentralGoogle Scholar Harrison, R., Papp, B., Pál, C., Oliver, S. G. & Delneri, D. Plasticity of genetic interactions in metabolic networks...