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• W2012307188 abstract "Summary Aberrant activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling is implicated in a number of haematological malignancies and effective JAK inhibitors may be therapeutically useful. We found that Gö6976, an indolocarbazole inhibitor of the calcium‐dependent isozymes of protein kinase C (PKC), inhibited interleukin 3/granulocyte‐macrophage colony‐stimulating factor‐induced signalling, proliferation and survival whereas Gö6983, a broad spectrum PKC inhibitor, had no such effects. Gö6976 was found to be a direct and potent inhibitor of JAK2 in vitro . Gö6976 also inhibited signalling, survival and proliferation in cells expressing the leukaemia‐associated TEL–JAK2 fusion protein and the myeloproliferative disorder (MPD)‐associated JAK2 V617F mutant. In primary acute myeloid leukaemia (AML) cells, incubation with Gö6976 reduced constitutive STAT activity in all cases studied. In addition, Akt and mitogen‐activated protein kinase phosphorylation were reduced in 4/5 FLT3 ‐internal tandem duplication (ITD) positive AML cases and 7/13 FLT3 ‐wild‐type (WT) cases. Expression of FLT3 ‐WT, ITD and D835Y in 32D cells showed that Gö6976 is also a potent inhibitor of WT and mutant FLT3. In AML cells, Gö6976 reduced the survival to 55 ± 5% of control in FLT3‐ITD cases and to 69 ± 5% in FLT3‐WT samples. These data may help identify clinically useful compounds based on the structure of Gö6976, which can be employed for the treatment of MPDs as well as AML." @default.
• W2012307188 created "2016-06-24" @default.
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• W2012307188 date "2006-09-28" @default.
• W2012307188 modified "2023-10-17" @default.
• W2012307188 title "Gö6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells" @default.
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• W2012307188 doi "https://doi.org/10.1111/j.1365-2141.2006.06291.x" @default.
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