GNF-2 is an aminopyrimidine-based, allosteric inhibitor of Bcr-Abl wih an in vitro IC50 activity of 70 nM. [1] GNF-2 exhibits preferential activity Bcr-Abl-expressing cells (138 nM) with little to no antiproliferative effects in a panel of Ba/F3 cells transformed with kinases such as Flt3 ITD, Tel PDGFRb, TPR Met, and Tel JAK1. In Bcr-Abl-transformed cells, GNF-2 induces apoptosis at concentrations as low as 1 uM at 48h, while parental Ba/F3 cells were unaffected at concentrations up to 10 uM. [2] GNF-2 also inhibits Bcr-Abl and Stat5 tyrosine phosphorylation at concentrations of 270 nM and 1 uM, respectively. Selectivity panel studies show that GNF-2 is inactive towards a range of serine/threonine (e.g. CDK1, cRAF, PDK1, PKA, PKB), receptor tyrosine (e.g. FGFR1/3, Flt1/3/4, HER1/2, KDR, c-Kit), and non-receptor tyrosine kinases (BTK, Lck, c-Src).
GNF-2 targets wild-type Bcr-Abl as well as many clinically-relevant imatinib (Gleevec)-resistant mutants eitehr alone or in combination with other Bcr-Abl inhibitors. GNF-2 is also known to inhibit Arg (Abl-related gene) kinase at a IC50 of 670 nM. [1]
Technical information:
| Chemical Formula: | C18H13F3N4O2 | |
| CAS #: | 778270-11-4 | |
| Molecular Weight: | 374.32 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | Benzamide, 3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl] | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | GNF-2, GNF 2 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Choi et al., N-Myristoylated c-Abl Tyrosine Kinase Localizes to the Endoplasmic Reticulum upon Binding to an Allosteric Inhibitor. J. Biol. Chem. 2009, 284(42), 29005-29014. Pubmed ID: 19679652 |
| 2. | Adrian et al., Allosteric inhibitors of Bcr-Abl-dependent cell proliferation. Nat. Chem. Biol. 2006, 2(2), 95-102. Pubmed ID: 16415863 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
