Reference Detail


Missing content? – Request curation!

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

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

Email us at :

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 British journal of haematology
Vol 135
Issue 3
Date 2006 Nov
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.


  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (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 a longer phrase which contains spaces "mtor c1483f"


  • 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.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Go6976 Go6976 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Go6976 Go 6976|Go-6976 FLT3 Inhibitor 61 JAK2 Inhibitor 16 PKC alpha Inhibitor 6 PKC beta Inhibitor 6 Go6976 binds and inhibits the calcium-dependent protein kinase C (PKC) isoforms, as well as Flt3, and mutant and wild-type Jak2, which may promote apoptosis and tumor regression (PMID: 8486620, PMID: 16956345, PMID: 32783140).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK2 V617F acute myeloid leukemia sensitive Go6976 Preclinical Actionable In a preclinical study, Go 6976 inhibited proliferation of cultured acute myeloid leukemia cells expressing the JAK2 V617F mutation (PMID: 16956345). 16956345