Chronic myelogenous leukemia (CML) is a hematological malignancy caused by a chromosomal rearrangement that generates a fusion protein, Bcr-Abl, with deregulated tyrosine kinase activity. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, is an allosteric inhibitor of Bcr-Abl that enters the myristate binding pocket at the base of the C-lobe in the Abl kinase domain. When used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. Findings in streptozotocin treated mice (diabetes model) demonstrated that GNF-5 prevented the loss of beta cells and the increase in blood glucose as well as increased insulin protein levels when compared with control mice. In addition GNF-5 inhibited the development of airway hyperresponsiveness and airway remodeling in mouse model of asthma.