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]