Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV-1-infected T lymphocytes in vitro

2010 ◽  
Vol 127 (7) ◽  
pp. 1584-1594 ◽  
Author(s):  
Mariko Tomita ◽  
Yuetsu Tanaka ◽  
Naoki Mori
Keyword(s):  
T Lymphocytes ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
Growth And Survival

scholarly journals In vitro evaluation of Aurora kinase inhibitor—VX680—in formulation of PLA-TPGS nanoparticles

2016 ◽  
Vol 7 (2) ◽  
pp. 025010 ◽  
Author(s):  
Thi Thuy Duong Le ◽  
Phuong Thu Ha ◽  
Thi Hai Yen Tran ◽  
Dac Tu Nguyen ◽  
Hoai Nam Nguyen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
In Vitro Evaluation

scholarly journals Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

2020 ◽  
Vol 177 (12) ◽  
pp. 2848-2859
Author(s):  
Li‐Na Zhang ◽  
Kunmei Ji ◽  
Yue‐Tong Sun ◽  
Yi‐Bo Hou ◽  
Jia‐Jie Chen
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Mast Cell Activation ◽  
Aurora Kinase Inhibitor

Toward In Vitro Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor

2019 ◽  
Vol 23 (10) ◽  
pp. 486-495 ◽  
Author(s):  
Sevim Dalva-Aydemir ◽  
Cemaliye Boylu Akyerli ◽  
Şirin Kılıçturgay Yüksel ◽  
Hilal Keskin ◽  
Mustafa Cengiz Yakıcıer
Keyword(s):  
Thyroid Cancer ◽  
Drug Design ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor ◽  
Epigenetic Drug

Combined Inhibition of Janus and Aurora Kinase Effectively Suppresses Proliferation of JAK2 V617F-expressing Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2813-2813
Author(s):  
Karoline Gäbler ◽  
Catherine Rolvering ◽  
Valérie Palissot ◽  
Guy J. Berchem ◽  
Iris Behrmann ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Jak2 V617f ◽  
Aurora Kinase ◽  
Signaling Proteins ◽  
Jak Inhibitor ◽  
Aurora Kinase Inhibitor ◽  
Aurora Kinase Inhibitors ◽  
Proliferation Assays

Abstract Abstract 2813 Background: A somatic point mutation in the Janus kinase 2 gene (JAK2) leading to the expression of the JAK2 V617F mutant occurs with high frequency in myeloproliferative neoplasm (MPN) patients (>95 % in polycythemia vera (PV), >50 % in essential thrombocythemia (ET) and primary myelofibrosis (PMF)). It confers constitutive activity to the kinase and results in cytokine hypersensitivity and a proliferative advantage of hematopoietic progenitor cells. These findings suggest that inhibiting JAK2 V617F may be therapeutically beneficial. Several JAK2 inhibitors are currently in clinical trials for the treatment of MPN, and first results show clinical improvements for PMF patients. However, since approximately 50 % of ET and PMF patients do not carry an activating mutation in JAK2, we speculate that the inhibition of signaling proteins other than JAK2 or in combination with JAK2 inhibition could be beneficial for these patients. Methods: We characterized compounds from different chemical classes, which previously have been published to be JAK(2) inhibitors. These compounds were compared in several assays using primary CD34+ cells from PV patients positive for the JAK2 V617F mutation and/or the JAK2 V617F-bearing cell line HEL. We used (quantitative) Western blot detections, in vitro kinase assays, proliferation assays, cell size measurements, cell cycle analyses and colony forming cell (CFC) assays to analyze the efficacy of the different inhibitors. Moreover, the IC50 values of the compounds were determined. Results: In total 15 published JAK2 inhibitors have been characterized in detail. As monitored in an in vitro kinase assay and by Western blot detection of phosphorylated signaling proteins, several compounds previously described as JAK(2) inhibitors did not target JAK2 V617F. However, some compounds, which turned out not to inhibit JAKs, showed growth-inhibitory effects on JAK2 V617F-positive cells. Such compounds could be used in combination with a specific JAK inhibitor in order to achieve beneficial effects on suppression of cell proliferation and induction of apoptosis. We could demonstrate that the combined application of a JAK inhibitor together with an Aurora kinase inhibitor was most promising: application of both Janus and Aurora kinase inhibitors in proliferation assays and CFC assays demonstrated a more effective suppression of growth than achieved by respective single treatments. Interestingly, we observed in the CFC assay that a JAK2 inhibitor seems to preferentially suppress the growth of erythroid colonies, while an Aurora kinase inhibitor preferentially blocks myeloid colony growth. Conclusion: Here we present a comparative analysis and a detailed biochemical characterization of numerous compounds from different chemical classes, all supposed to be JAK(2) inhibitors. We confirmed JAK(2) inhibitory activity for several compounds but not for all. In addition, we identified some compounds, which effectively inhibited the proliferation of JAK2 V617F-bearing cells without targeting JAK2. Thus, combined inhibition of JAK2 and other kinases may represent a promising therapeutic strategy. In particular, we suggest that a combination of Janus and Aurora kinase inhibitors might be beneficial for the treatment of MPN patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High NRF2 Levels Correlate with Poor Prognosis in Colorectal Cancer Patients and with Sensitivity to the Kinase Inhibitor AT9283 In Vitro

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1365 ◽  
Author(s):  
Laura Torrente ◽  
Gunjit Maan ◽  
Asma Oumkaltoum Rezig ◽  
Jean Quinn ◽  
Angus Jackson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Related Factor ◽  
Aurora Kinase Inhibitor ◽  
Poor Patient ◽  
Patient Prognosis ◽  
Colorectal Tumours

Aberrant hyperactivation of nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2) is a common event in many tumour types and associates with resistance to therapy and poor patient prognosis; however, its relevance in colorectal tumours is not well-established. Measuring the expression of surrogate genes for NRF2 activity in silico, in combination with validation in patients’ samples, we show that the NRF2 pathway is upregulated in colorectal tumours and that high levels of nuclear NRF2 correlate with a poor patient prognosis. These results highlight the need to overcome the protection provided by NRF2 and present an opportunity to selectively kill cancer cells with hyperactive NRF2. Exploiting the CRISPR/Cas9 technology, we generated colorectal cancer cell lines with hyperactive NRF2 and used them to perform a drug screen. We identified AT9283, an Aurora kinase inhibitor, for its selectivity towards killing cancer cells with hyperactive NRF2 as a consequence to either genetic or pharmacological activation. Our results show that hyperactivation of NRF2 in colorectal cancer cells might present a vulnerability that could potentially be therapeutically exploited by using the Aurora kinase inhibitor AT9283.

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