Kelperoid kinase 1(PLK 1) is an important target. Because of its required function, anticancer therapy can splinter cell and improve the sensitivity of cancer cell inactivation. Several drugs targeting plk 1 have appeared, including bi-2536 and ZK- thiazolidinone (TAL). These inhibitors and inhibition of cell mitosis and phenotype are consistent with other methods of down-regulating Plk 1 bi-2536 and pharmacological optimization simulation (bi-6727), which show the hope of preliminary clinical trials. The inhibition ability of chemical gene system has also been developed. In this system, immortalized human retinal pigment epithelial cells with two copies of PLK 1 gene deletion were recombined by localization and cre-lox mediation. In enzyme Cre-mediated excision, Plk 1 -/- clones cannot be cloned unless they complement the expression of Plk 1, whether it is wild-type (plk 1wt) or compound mutation (L130g C67V; ; Then plk 1as). The latter mutation allows Plk 1 to accept a large volume of purine analogues, such as adenosine triphosphate competitive inhibitors, by expanding the active site of kinase. We report here that these mutations also have unexpected effects on desensitized Plk 1 clinically useful inhibitors such as bi-2536 and TAR. (All chemicals used in the structure are shown in the supplementary drawing 1. )

When examining bi-2536 with anti-proliferative activity, we found that the compound strongly inhibited the growth of plk 1wt cells, but had little or no effect on plk 1as cells (Figure 1 2). In order to determine whether to change the inhibitor bi-2536 with unique efficacy, we used Plk 1 inhibitors with different structures to carry out similar growth challenge experimental environment. Thirdly, we have observed that plk 1as cells are significantly different from their counterparts in gene plk 1wt (digital integrated circuit, development). In order to understand the depth and breadth of drug resistance of inhibitors, we asked about various readings and activities in the body. PLK 1 needs to be in the whole mitosis, good function, centrosome maturation, bipolar spindle assembly, stable attachment of active microtubules, and start cytoplasm. All these procedures proved to be qualitative and quantitative for two plk 1 targeted inhibitors. For example, plk 1as cells continue to recruit γ -tubulin (the basic expression of centrosome maturation) and centrosomes of bi-2536 (Figure 2) and Tal (Figure B) existing in bipolar spindles. Similarly, the ability to over-phosphorylate Bubr 1 (a key factor, stable attachment of active microtubules) was not impaired, which was reflected in the continuous flow transfer electrophoresis of peptides such as BubR 1 (Figure 2). According to this extensive defect, these two compounds cause mitotic arrest of PLK 1G (but not plk 1as cells). Look at their circular appearance and phase contrast microscope (Figure 4).