Targeting protein kinases

Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor

“…Moreover, the strategies in targeting APE/Ref-1 for cancer chemotherapy or sensitization have certain advantages. As signaling proteins do not act in isolation but form an intricate network in the cell, compounds targeting multifunctional proteins would not only affect one pathway but also will interfere with multiple downstream targets/signals (71). APE/Ref-1 is a multifunctional protein and seems to be a central protein forming a unique link with DNA base excision repair, redox-activating transcription factors, and oxidative stress (2), so targeting APE/Ref-1 should be a useful strategy to enhance the therapeutic potential of many compounds and potentially in many other malignancies as well.…”

“…For example, advances have been made with cancer therapeutic agents through targeting protein kinases for specific inhibitor design from protein structures (70,71). Using sophisticated computer programs to model the threedimensional structure of Ref-1/APE protein and virtual screening software to dock molecules from drug libraries to the protein, we screened compounds that would interfere with Ref-1 protein.…”

RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors

“…Aberrantly active protein kinases have been implicated in a variety of cancers and represent an important class of drug targets (Blume-Jensen and Hunter, 2001;Cohen, 2002;Dancey and Sausville, 2003;Melnikova and Golden, 2004). Currently marketed biologics and small molecules targeting kinases are proving effective against well-characterized cancers.…”

The influence of phase II conjugation on the biological activity of flavonoids

“…The most frequently reported association of flavonol intake with human health is an inverse correlation with the occurrence of cardiovascular diseases and related risk factors [95][96][97][98][99]. A positive correlation of flavonol intake and cognitive performance in middle-aged adults is reported for language and verbal memory.…”

“…Chronic inflammation is regarded as a risk factor for many diseases, such as metabolic disorders and cardiovascular diseases [94]. Flavonoids are reported to have anti-inflammatory effects [95][96][97] and it is of interest to note that protein kinases play a fundamental role in inflammation [98][99][100]. In recent in vitro studies, glucuronidation is reported to reduce the anti-inflammatory effect of quercetin in macrophages (see Table 7.2).…”