The development of multikinase inhibitors for the treatment of selected cancers

开发用于治疗特定癌症的多激酶抑制剂

• 批准号: 10469243
• 负责人: Craig Thomas
• 金额: $ 18.78万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469243
• 关键词: Acute Myelocytic Leukemia; Chemicals; Clinical; Collaborations; Development; Disease; Disease model; Dysmyelopoietic Syndromes; Enzymes; FLT3 inhibition; FLT3 inhibitor; Goals; IRAK1 gene; Malignant Neoplasms; Mutation; Pediatric Hospitals; Pharmaceutical Preparations; Phosphotransferases; Plague; Research Personnel; Scientist; Technology; Work; cancer type; design; in vitro activity; in vivo Model; inhibitor/antagonist; innovation; kinase inhibitor; leukemia; screening; small molecule; therapeutic development

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.

化学技术研究人员开发了其他科学家可以用来从事治疗开发创新的小分子和筛选方法。小分子激酶抑制剂在几种癌症的适应症中发现效用为药物。最近，与Sarczynowski Lab（辛辛那提儿童医院）的合作建立了小分子IRAK抑制剂在骨髓增生综合征（MDS）中的潜力。在这项工作的扩展过程中，我们确定已知的IRAK抑制剂具有独特的活性与急性髓细胞性白血病和脊髓细胞性白血病癌系。该代理具有强大的活性，而包括FLT3，PDGRF和IRAK在内的几种激酶，其体外活性超过了该结构域中的现有药物。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当前鼠疫临床上有效的FLT3抑制剂的选定突变，因此限制了它们的效用。