【摘要】 双特异性酪氨酸磷酸化调节激酶1A(Dual-Specificity Tyrosine Phosphorylation Regulated Kinase 1A,DYRK1A)被认定为重要的抗神经性退行性疾病的治疗靶点。该研究基于文献报道的117个DYRK1A杂环类抑制剂，采用遗传算法（Genetic Algorithm,GA）联合多元线性回归（Multiple Linear Regression,MLR）方法，建立了具有良好稳健性及预测能力的定量构效关系（Quantitative Structure-Activity Relationship,QSAR）模型，揭示了影响该类抑制剂活性的分子描述符包括SpAD＿B(m),GATS5m,nCb-和B02[C-O]，为新型DYRK1A抑制剂的开发提供理论基础和设计思路。更多还原

【Abstract】 Dual-Specificity Tyrosine Phosphorylation Regulated Kinase 1A(DYRK1A) has been considered as an important therapeutic target of neurodegenerative diseases. Based on 117 heterocyclic DYRK1A inhibitors reported in the literature, Genetic Algorithm(GA) combined with Multiple Linear Regression(MLR) method were used to develop a robust and predictive QSAR model. The optimal model shows that the molecular descriptors affecting DYRK1A inhibitory activity of include SpAD＿B(m), GATS5m, nCb-and B02[C-O]. All the results provide theoretical basis and optimization clues the development of novel DYRK1A inhibitors.更多还原