MOLECULAR INTERACTIONS REGULATING INTRACELLULAR SIGNALING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 EGFR激酶的突变激活是人类非小细胞肺癌(NSCLC)的重要原因。小分子药物Iressa和Tarceva对治疗某些类型的EGFR突变引起的疾病有效，但由于EGFR激酶中出现新的突变T790M，使其对当前药物产生耐药性，因此疗效持续时间有限。我们已经确定了几种新的化合物，它们可以特异性地抑制携带T790M突变的EGFR激酶。经过优化后，这些新化合物很有可能用于治疗耐药的非小细胞肺癌。在这个子项目中，我们的目标是解决与这些新化合物形成的复合体中的耐药EGFR突变激酶。这项研究将为这些化合物的优化奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mutational activation of EGFR kinase is an important cause of human non-small cell lung cancer (NSCLC). Small molecule drugs, Iressa and Tarceva, are effective in treating the disease caused by some types of the EGFR mutations, but the duration of efficacy is limited due to the emergence of a new mutation T790M in the EGFR kinase that confers resistance to the current drugs. We have identified several new compounds that can specifically inhibit EGFR kinase bearing the T790M mutation. There is a good chance that these new compounds can be used to treat the drug-resistant NSCLC after optimization. In this subproject we aim to solve the drugresistant EGFR mutant kinase in complex with these new compounds. This study will form the basis for optimization of these compounds.