Interestingly, DHPCC 9 seems to target Pim 1 and Pim 3 slightly more efficientl

Interestingly, DHPCC 9 seems to target Pim 1 and Pim 3 slightly more efficiently than Pim 2. This selectivity is in line with similar observations from several other Pim inhibi tors, as recently discussed, INNO-406 価格 Even though Pim 1 and Pim 3 are more closely related to each other than to Pim 2, structural models are unable to explain the observed differences in their sensitivities. In cell based assays, the activities of inhibitors are not expected to be as high as under in vitro conditions with purified compounds. Thus, the micromolar IC50 values observed in FD Neo and FD Pim44 cells can be considered promising, especially since they were obtained using complete medium containing 10% serum.<br><br> Cytotoxicity assays with some other Pim inhibi tors have been carried out in the presence of lower or no serum levels, which probably has decreased Lapatinib ic50 the viability of the cells and also enhanced bioavailability of the inhibitors and consequently lowered their IC50 values. Indeed, more pronounced effects were observed also in our assays with DHPCC 9, when cells were grown in the absence of serum. Yet it is likely that the efficiency of the Pim inhibitor can be further improved by using DHPCC 9 as a scaffold for production of additional, more potent derivatives, which could be useful not only as research tools, but also as lead compounds in development of drugs against Pim overexpressing tumors. Since DHPCC 9 has been shown to be highly efficient in reducing the motility of Pim overexpressing cancer cells, derivatives of DHPCC 9 might be able to prevent tumor metastasis and or angio genesis.<br><br> Moreover, since we and others have recently shown that Pim kinases are involved in development of resistance against radiation therapy or chemotherapy, combinations of Pim inhibitors together with other anticancer therapy methods are expected purchase LY2109761 to lead to most efficient therapeutic approaches. Even though Pim kinases have been implicated to have prognostic roles in several types of solid cancer, there is still controversy in the literature on whether or not high levels of Pim expression are of disadvantage for prostate cancer patients, This may be partly due to heterogeneity of the samples and to the fact that in none of the studies published so far have expression levels for all three Pim kinases been analysed in parallel. It is also clear that overexpressed Pim kinases alone are unable to transform cells, but require collaboration e.<br><br> g. with Myc oncoproteins. Interestingly in this regard, coexpression of Pim 1 and c Myc in human prostate tumors has recently been associated with higher Gleason grades than overexpression of either one alone, suggest ing that these oncoproteins synergize to induce advanced prostate carcinoma, While our work was in progress, silencing of Pim 3 was reported to reduce endothelial cell spreading, migration and vascular tube formation, providing further support to our hypothesis that Pim kinases can stimulate metastatic and or angiogenic potential of can cerous cells.