Notyps Ted in the initiation and / or maintenance of the malignant Ph Resistance to chemotherapy and targeted Celecoxib Celebra microtubules, as paclitaxel.5, Aurora kinase A contr 12,13,14 The many stages of mitosis, such as entry and mitotic spindles and bipolar output to centrosome localized early G2 phase.5, 15 has As such, inhibition of Aurora-A kinase activity t been found to cause centrosome separation and maturation of M ngel, spindle aberrations, cell cycle arrest and apoptosis.16 In particular, Aurora A kinase interacts with p53 at multiple levels, with evidence that the p53-negative tumors are more sensitive to inhibitors of Aurora kinase A and p53 positive tumors.17 1.3 Relevance of Aurora B kinase levels of Aurora B kinase has been in many tumor cell lines, including normal hours dermatological malignancies were found.
overexpression of Aurora B kinase, Aurora-like kinase Green et al. Expert Opin Drug Discov page 2. Author manuscript, increases available in PMC 2012 1 M rz. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH overexpression c-Met inhibition was chromosomal instability at t and aneuploidy.11, 18 Aurora B kinase Akt has been linked as a catalytic component of the chromosomal passenger complex and play an r The key to the alignment of chromosomes, chromosome condensation, spindle and cytokinesis.4, lifts the inhibition of Aurora B 6.16-kinase activity t the controlled station the spindle and mitotic exit without causing premature cytokinesis. As a result, polyploid cells Of m for may have for the inhibition of cell growth and / or apoptosis, dependent Ngig of the cell line.
Neutropenia is an hour INDICATIVE consequence of the inhibition of Aurora B kinase, whether individually or in a number n North part inhibited inhibition.19 1.4 Relevance of the aurora kinase C is relatively little known about the aurora kinase C, is different from his r Meiosis in the testes. New data show r Potential in tumorigenesis, m for may have due to the activity T Similar to Aurora B kinase.8 The r In tumorigenesis remains controversial. Currently there are no C-Aurora kinase inhibitors specific development, the nkt Aufkl Tion of the effects of Aurora kinase C specific cancer Descr. 2.0 ground Tze and therapeutic targeting of Aurora kinases All AKIS currently being developed for clinical use are inhibitors of small molecules on the ATP-binding pocket through hydrogen bonding, hydrophobic, aromatic and van der Waals interactions to bind.
By definition, all AKIS are wettbewerbsf ATP binding compatibility available and reversible. AKIS Many, including specific isoform AKI inhibits all three Aurora kinases through the highly conserved catalytic center with the Aurora kinases. However, PMI inhibit Aurora kinase isoforms with Ki values of the differential, creating a selective activity of t. Although specific inhibition of Aurora-A kinase Aurora B kinase-or-Ph A genotype different from each other, there is no agreement on the induced therapeutic targeting of Aurora kinases. Originally, the Aurora A was specific targeting as lebensf Seen Higer therapeutic target, given its R In tumorigenesis.
Pr Clinical data has established that the inhibition of Aurora A and Aurora B kinases simultaneously produces a biological effect Similar to the Ph Phenotype and the inhibition of Aurora kinase B alone.20 However, no clinical data in humans have shown specific AKIS to be more or less therapeutic value than multi-or pan-Aurora inhibitors. The detection of the clinical activity t of Aurora kinase inhibitors in B Sartigkeit and study design are shown in Table 2. New data show that combined