Transportation. MLN8054 MLN8054 is an ATP-competitive inhibitor discovered recently Aurora kinase family, it is very specific but Aurka h Can inactivate here AURKB concentrations. MLN8054 40 times more selective for Aurka AURKB that they are not degraded or regulate the bottom, but inhibits Aurka phosphorylation. MLN8054, at h Higher concentrations, TKI258 VEGFR inhibitor inhibits the phosphorylation of histone H3, an indication of the inhibition AURKB. It induces abnormal mitotic spindles, G2 / M accumulation, cell death by apoptosis, and Ph Phenotypes consistent with inhibition Aurka. Cells treated with MLN8054 develop an abnormal DNA content. These anomalies treatment with MLN8054 pronounced Gter be over time. Unlike the pan Aurora kinases MLN8054 Aurka more specific reason of their R Is ability to inhibit the phosphorylation of T288, growing the cells into mitosis in vivo.
We recently reported the induction of TAp73 PI-103 protein and various pro-apoptotic gene, PUMA, NOXA and p21 in cells that MLN8054 by various types of p53-deficient tumors. p53-deficient cells are resistant to chemotherapy. This observation that MLN8054 induced TAp73 k nnte To be advantageous in targeting tumors without p53. MLN8237 MLN8237 is an inhibitor of the second generation and has recently joined Aurka Phase I / II clinical trials. It inhibits Aurora A with an IC50 of 1 nM in biochemical assays and has 200 times the selectivity of t for more Aurka AURKAB in cellular Ren assays. A wide-receptors and ion channels Le showed no significant cross-reactivity t. The compounds block the growth of various tumor cell lines with GI50-values as low as 16 nm.
The growth inhibition with abnormalities of the mitotic spindle, the polyploid Anh Ufung of mitotic cells Dying and Dar al. Mol Cancer Ther 6 page. Author manuscript, increases available in PMC 2011 2 February. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH and apoptosis. It is absorbed orally and rapidly available. Doses in a transient inhibition of histone H3 phosphorylation is observed by a significant increase in the phosphorylation of histone H3 followed. Maximum efficiency in vivo in various xenograft was obtained with oral doses of 20mg/kg twice t Was like for 21 consecutive days, even when other treatments are also effective.
MLN8237 in combination with rituximab was found that tumor burden in an additive mechanism and / or synergistic effects in several models of diffuse large To reduce cell B-cell lymphoma tumor cells. PHA PHA 680632 680632 is a potent inhibitor of Aurora kinase family, with an IC50 of 27, 135 and 120nmol / L for Aurora A, B and C and shows the st Strongest cross-reactivity T to FGFR1. PHA 608632 is as potent antiproliferative activity T have a wide range of cancer cell lines. PHA-680 632 inhibits autophosphorylation of T288 and Aurka AURKB mediated phosphorylation of histone H3 Ph genotypes That are consistent with inhibition of Aurka and AURKB. The inhibition of PHA-680 632 Aurka in p53 / HCT116 cells by treatment response in radiotherapy followed erh Hte apoptosis. This additive effect of PHA-680632 and IR radiation galv GERTES tumor growth in xenograft model, inhibition of colony formation and polyploid Induced death.
PHA680632 caused additive interaction induced with radiation with respect to cell death by p53 non-functional cells. Additivity t may be of advantage in such combinations of chemotherapy radiation therapy. PHA680632 and radiation therapy could be used fa Is simultaneous or temporal N Hey, potentially endless acute complications S or healthy tissue. PHA is PHA 739358 739358 super power Stronger than his VORG singer and PHA-680 632 inhibits all three Aurora kinases A, B and C with IC50 of 13, 79 and 61nmol / l. It has a high cross-reactivity t mutates with other kinases, or cancer of the Li overexpressed