Eg5, the product of Kif11 gene, also known as kinesin spindle protein, is a motor protein involved in proper establishment bipolar mitotic spindle. Eg5 one 45 different kinesins coded human genome superfamily. Over last three decades has attracted great interest promising new target. The identification monastrol specific inhibitor ATPase activity domain inhibiting microtubule motility vitro and...

Introduction: One mechanism of cell cycle manipulation and mitotic catastrophe is arrest at G2/M phase of cell cycle. Cabazitaxel, a mitotic inhibitor agent, is a second-generation semisynthetic taxane. An expected anti-neoplastic effect of Cabazitaxel is cell cycle perturbation and alteration of microtubule dynamics. In contrast to other taxane compounds, Cabazitaxel is a poo...

Mitosis inhibitors, which include antimicrotubule drugs, are chemotherapy agents that induce the arrest and apoptosis of mitotic cells. Mitotic slippage, in which mitotically arrested cells exit mitosis, limits the effectiveness of mitosis inhibitors. We have discovered that the CRL2ZYG11A/B ubiquitin ligase promotes mitotic slippage. The combination of antimicrotubule drugs and a CRL2ZYG11A/B ...

Eribulin is a unique microtubule inhibitor with mitotic and nonmitotic mechanisms of action. has substantial activity in patients pretreated (anthracycline taxane) advanced or metastatic breast cancer was confirmed by large-scale phase III clinical trials. We review recent pharmacological findings eribulin use cancer, particularly highlighting difficult-to-treat aggressive disease safety data s...

The challenging possibility of selectively inducing mitotic death in tumor cells by combining genotoxic agents with the inhibition of G2 checkpoints of the cell cycle is the subject of intensive investigation. We show that very low concentrations (3.5 and 5 nM) of okadaic acid induce mitotic death in two glioblastoma cell lines, in the absence of genotoxic agents. At the concentrations used, th...

We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 A resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg2+ x ADP, reveals that monastrol confers inhibition by "induced-fitting" onto the protein some 12 A away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pock...

conclusions treatment strategies in acquired hemophilia are based on two major objectives. during the acute stage, effective control of bleeding is critical. the ultimate therapeutic goal during the subacute phase is the elimination of the inhibitors targeting factor viii. here, we present this case and will review current literature regarding therapeutic approaches to this rare condition in th...

bypassing agents are the most commonly used medicines for the treatment of hemophilia patients with inhibitors. the aim of this study is to identify the cost components of management of bleeding vents in hemophilia patients with inhibitors in iran. this study is a cross-sectional study using a bottom-up approach to determine the cost components of treatment of hemophilia patients with inhibitor...

The aim of this study was to investigate the mechanism of inhibition of Eg5 (kinesin spindle protein), a mitotic kinesin that plays an essential role in establishing mitotic spindle bipolarity, by the novel small molecule inhibitor K858. K858 was selected in a phenotype-based forward chemical genetics screen as an antimitotic agent, and subsequently characterized as an inhibitor of Eg5. K858 bl...

Microtubule-poisoning drugs, such as Paclitaxel (or Taxol, PTX), are powerful and commonly used anti-neoplastic agents for the treatment of several malignancies. PTX triggers cell death, mainly through a mitotic arrest following the activation of the spindle assembly checkpoint (SAC). Cells treated with PTX slowly slip from this mitotic block and die by mitotic catastrophe. However, cancer cell...