Different tested PKC isoforms, PKA, PKG, CaM kinase II, MLC kinase, CK2, EGFR tyrosine kinase, p56lck, p56lyn, p60c-src, and insulin receptor tyrosine kinase, were also not inhibited. = 0.4 M) in an ATP-competitive manner [154,155]. Other flavonoids were also described as very Maxacalcitol potent inhibitors of Ser/Thr protein kinases, like apigenin, chrysoeriol, luteolin, pedalitin, fisetin, and alpinetin. Compared to quercetin, apigenin and luteolin experienced comparable or slightly better effects on GSK-3 . From such results, it can be predicted that flavonoids with larger side chains have lower activity on GSK-3. Agullo et Maxacalcitol al.  compared the activity of several flavones and flavonols on PI3K, EGFR kinase, and PKC. Both serine/threonine kinases, PI3K and PKC, were inhibited by a similar profile. The most hydroxylated flavonoids (myricetin, quercetin, and luteolin) were the most potent inhibitors, whereas compounds with only two hydroxyl groups (galangin and chrysin) possessed almost no effect on the kinase activities. These findings did not hold true for EGFR tyrosine kinase. The observed structureCactivity relationship was reverse to that of PI3K and PKC . Flavonoid compounds with less hydroxyl groups (apigenin and kaempferol) showed higher inhibitory potential towards EGFR kinase than quercetin and luteolin. The first results using flavonoids as protein kinase CK2 inhibitors were explained by Li et al. and Lolli et al. [144,145]. As we have demonstrated in our former publications, flavonoids isolated from herb materials are potential inhibitors of protein kinase CK2. We tested more than 20 compounds (e.g., apigenin, pedalitin, and chrysoeriol) for their effect on different CK2 isoforms and showed that CK2 was the most sensitive towards examined compounds [146,147]. Chrysoeriol was found to be the most encouraging flavonoid, with IC50 values in the low nanomolar range. Most other tested flavonoids possessed an inhibitory effect, with IC50 values between 0.2 and 10 M for free catalytic CK2 subunits and between 1 and 20 M for the CK2 holoenzymes. Quercetagetin, the major flavonoid in marigold, was characterized as a potent and selective inhibitor of PIM1 kinase . It was Maxacalcitol shown that this IC50 value for PIM1 was 0.34 M, while the respective values for other tested serine/threonine kinases (c-Jun, PKA, Aurora-A, c-Raf, and PKC) were 9- to 70-fold higher. Besides quercetagetin, other flavonoids, CSF2RA like gossypin, myricetin, fisetin, and apigenin, decreased the PIM1 activity with IC50 values below 1 M. Quercetin, kaempferol, luteolin, and morin still showed very good effects around the kinase activity with IC50 values between 1 and 3 M. Cyclin-dependent kinases (CDKs) are involved in the regulation of cell cycles and transcription. Several flavonoids have been found to inhibit CDK9. The most potent inhibitor with an IC50 value in nanomolar concentrations (190 nM) was found to be wogonin, which also inhibited CDK2 and 7, but at much higher concentrations of 1 1.46 and 12.3 M, respectively . Other flavonoids showed weaker effects on CDK1, 5, and 6, as summarized by Jain et al. . Genistein was ineffective when tested against CDK2 and 4, whereas fisetin was detected to reduce the CDK1, 5, and 6 activities with IC50 values below 1 M. Kaempferol and quercetin, being good inhibitors in cases of other serine/threonine kinases, showed weak effect towards CDK 1, 5, and 6, as well as CDK2 and 4, respectively, with IC50 values between 20 and 60 M. Luteolin, apigenin and chrysin were identified as good inhibitors, with values below 10 M. 3.1.2. Phenolic Acids Within the class of polyphenolic compounds, 30% belong to phenolic acids. They are divided into two major groups: hydroxybenzoic and hydroxycinnamic acids. Hydroxybenzoic acids are simple, aromatic acids possessing strong antioxidative and anticancer activities. The most important associates are tannic, gallic, and ellagic acid. Physique 4 shows the structures of some users of that class. Open in a separate window Physique 4 Structures of phenolic acids. Tannic acid is an ingredient of tara, nutgall tree, Aleppo oak, and Sicilian sumac. It was shown that a concentration.