Expression profiling of the effect of treatment with GNF-7 on mutant NRAS-positive leukemia cell lines

The complexity of RAS signaling makes targeting RAS challenging. We therefore hypothesized that inhibiting a combination of downstream targets of RAS may potentially lead to an effective therapeutic intervention. We performed a high-throughput chemical screen using a library consisting of multi-targeted inhibitors with the expectation that one or more inhibitors would likely- due to their broad spectrum inhibitory potential- hit critical targets of mutant NRAS. We identified GNF-7, a multi-targeted kinase inhibitor that proved to have high selectivity and sensitivity for leukemia cells with NRAS mutations both in vitro and in vivo.

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