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，其他科学家可以使用这些方法在治疗开发中进行创新。小分子激酶抑制剂在几种癌症适应症中被用作药物。最近，与Sarczynowski实验室(辛辛那提儿童医院)的一项合作确定了小分子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抑制剂对急性髓系白血病和粒单核细胞白血病癌细胞具有独特的活性。该试剂对包括Flt3、PDGRF和IRAK在内的几种激酶具有较强的体外活性，其体外活性超过该领域现有的药物。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选定的突变，这些突变目前困扰着临床上具有活性的Flt3抑制剂，因此限制了它们的用途。

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.