The development of multikinase inhibitors for the treatment of selected cancers

化学技术研究人员开发小分子和筛选方法，其他科学家可以用来追求治疗开发的创新。小分子激酶抑制剂作为药物在几种癌症适应症中发现了效用。最近，与Sarczynowski实验室（辛辛那提儿童医院）的合作确定了小分子IRAK抑制剂在骨髓增生异常综合征（MDS）中的潜力。在这项工作的延伸中，我们已经确定了一种已知的IRAK抑制剂对急性髓性白血病和骨髓单核细胞白血病癌症细胞系具有独特的活性。该试剂对包括Flt3、PDGRF和IRAK在内的几种激酶具有强活性，其体外活性超过该领域的现有药物。我们目前正在评估这些疾病的体内模型中的候选小分子。重要的是，这些药物似乎克服了目前困扰临床活性Flt3抑制剂的选定突变，因此限制了它们的效用。

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.