芳基磺酰胺类丙酮酸激酶M2激动剂的基于多复合物的药效团模型和定量构效关系

doi:10.3866/PKU.WHXB201305152

Abstract

Abstract:

Pyruvate kinase M2 (PKM2) is well-known as a potential target for cancer therapy. In this study, the multicomplex-based pharmacophore (MCBP)-guided method was used to generate a comprehensive pharmacophore of PKM2 kinase based on a collection of crystal structures of PKM2- activator complex. This model was successfully used to identify the bioactive conformation and align 62 structurally diverse aryl-sulfamide derivatives. Quantitative structure-activity relationship (QSAR) analyses were performed on these PKM2 activators based on MCBP-guided alignment. With the comparative molecular field analysis (CoMFA) model, the cross-validated value (q²) was 0.545, and the non-crossvalidated value (r²) was 0.966. With the comparative molecular similarity indices analysis (CoMSIA) model, q² and r² were 0.653 and 0.987. These results may provide important information for further design of novel PKM2 activators.

Key words: Aryl-sulfamide derivative, Pyruvate kinase, Pharmacophore, Comparative molecular field analysis, Comparative molecular similarity indices analysis

MSC2000:

O641

CHEN Zheng-Jun, JIANG Qing-Lin, HE Gu, HAN Bo, GUO Li. Multicomplex-Based Pharmacophore and QSAR of Aryl-Sulfamides as Pyruvate Kinase M2 Activators[J].Acta Phys. -Chim. Sin., 2013, 29(08): 1793-1803.

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Multicomplex-Based Pharmacophore and QSAR of Aryl-Sulfamides as Pyruvate Kinase M2 Activators

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