The development of multikinase inhibitors for the treatment of selected cancers

National Center For Advancing Translational Sciences

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Abstract

Chemical Technology researchers develop small molecule and screening approaches that other scientists can use to pursue innovations in therapeutic development. Small molecule kinase inhibitors are finding utility as drugs in several cancer indications. Recently, a collaboration with the Sarczynowski lab (Cincinnati Childrens Hospital) established the potential of small molecule IRAK inhibitors in Myelodysplastic syndrome (MDS). In an extension of this work, we have established that a known IRAK inhibitor possesses unique activity versus acute myeloid leukemia and myelomonocytic leukemia cancer lines. The agent possesses strong activity versus several kinases including Flt3, PDGRF and IRAK with in vitro activity surpassing existing drugs in this domain. We currently are evaluating candidate small molecules within in vivo models of these diseases. Importantly, these agents appear to overcome selected mutations that current plague clinically active Flt3 inhibitors and, therefore, limit their utility.