Ytic part of the Chromosomal Passenger Complex and play an r The key to the alignment of chromosomes, chromosome condensation, spindle and cytokinesis.4, 6.16 inhibition of Aurora B kinase activity raises the t the Post team of professionals of the spindle and leads to premature exit without mitotic cell AC480 HER2 inhibitor division. 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, BMS-540215 VEGFR inhibitor 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 induces the 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 the combination with spindle poisons such as taxanes and vinca alkaloids, with an Aurora kinase inhibitor k Synergistic.14 can be 21 Also, due to the interaction of the kinase Aurora B, histone H3, histone deacetylase inhibitors with combination with AKIS can prove therapeutic dosage synergistic.22 Aurora kinase-specific agents can be difficult to show that h higher doses of AKIS can lead to an inhibitory effect pan Aurora. 2.1 The selective inhibitors of Aurora A kinase and ENMD 981 693 2.1.1 ENMD 2076 The molecule was originally described as ENMD 981 693 was developed ENMD 2076, the tartrate salt of L ENMD 981,693.23 ENMD 2076 is selective for Aurora A kinase ENMD 981 693, with an IC50 value of 14 nm for Aurora kinase A and 350 Nm of Aurora-B kinase, respectively.24 In addition, ENMD 2076 also inhibits FGFR3, PDGFR, VEGFR1, and a potent inhibitor of FLT3 with IC 50 values of 0.04 M. 21 clinical studies of pre ENMD 2076 in mouse models have promising results for multiple myeloma , breast cancer, leukemia shown chemistry and cancer. 24,25,26,27 In addition, several Phase I and II trials are currently underway in ov