Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (16956345)
Authors Grandage VL, Everington T, Linch DC, Khwaja A
Title Gö6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells.
Journal Vol Issue Date Pages Journal Short Title
British journal of haematology 135 3 2006 Nov 303-16 Br J Haematol
URL
Abstract Text 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.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.