The man is without precedent, already achieved the distinction of being the leading cause of death and economic burden world.1, BMS-536924 468740-43-4 2 Cancer is characterized by an uncontrollable proliferation EAA leads to a malignant Ph Genotype. Mitosis is a critical step in cancer cell proliferation and has many redundant systems and control point The contr Lant important steps in the process. The Aurora kinase family play an R Important in maintaining the fidelity of mitosis. This is the theory that the anti-cancer benefits may be derived from inhibition of Aurora kinase activity of t, leading to the development of several Aurora kinase inhibitors operate. 1.
1 The Aurora kinase Aurora kinases are a family of oncogenic serine / threonine kinases involved in mitotic phase of the cell cycle, acting to maintain the mitotic spindle to establish bipolar spindle formation, SKI-606 SRC inhibitor the orientation of the mitotic spindle to centrosomes, the centrosome separation, mitosis and cytokinesis followed checkpoint.3 are 4,5,6 Aurora kinases essential for accurate chromosome division and organized for each daughter cell. In addition, Aurora kinases are frequently in tumor cells that overexpressed particularly those with high growth fractions. There are three known Aurora kinases in human tissues and non-neoplastic neoplastic. Aurora kinases A and B are expressed in all tissues in the world, w While Aurora-C kinase is predominantly expressed in the testis, to participate in meiosis. But recent research has Aurora kinase C activity of t with tumor formation in somatic tissues and perhaps cancer relevant target.
3, 7,8 All three Aurora kinases have significant sequence and structural homology and overlapping gene expression in conjunction with catalytic Dom ne, genomic L length and kinase activity of t, although the cellular other functions and end portions of each differ.9 N, 10 Inhibition of Aurora kinase activity of t leads to catastrophic failure mitosis, such as M deficiencies in of cytokinesis, centrosomes misaligned, and malformation of the mitotic spindle that their H are hepunkt in apoptosis.10, 11 different compounds in the development of capital from the anti-cancer effects of inhibition of Aurora kinase activity of t. 1.2 Relevance of Aurora A kinase Aurora-A kinase is h Frequently in many epithelial tumors, cancers and tumors of solid organs verst RKT.
Aurora A kinase is in the initiation and / or maintenance of the malignant Ph Notyps and resistance to chemotherapy targeting microtubules associated, as paclitaxel.5, Aurora kinase A 12,13,14 contr The different stages of mitosis as mitotic entry and exit and bipolar spindles, st Amplifier localized to the centrosome may need during the early G2 phase. 5.15 Sun Aurora inhibition of Aurora A kinase activity of t has been shown to centrosome separation and maturation of M Ngel, spindle aberrations, cell cycle arrest and cause apoptosis.16 In particular, A kinase interacts with p53 at multiple levels, with evidence that p53-negative tumors more sensitive to Aurora kinase inhibitors p53 positive tumors.17 1.3 Relevance levels of Aurora B kinase levels of the kinase Aurora B have been found in many tumor cell lines, including normal hours dermatological malignancies.
overexpression of Aurora B kinase, Aurora-like kinase Green et al. Page 2 Cancer Drug Discov Pat last. Author manuscript, increases available in PMC 15th February 2011. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH overexpression was chromosomal instability at t and aneuploidy.11, 18 Aurora B kinase Akt has been linked as a Catal