Citation: 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 Physico-Chimica Sinica, ;2013, 29(08): 1793-1803. doi: 10.3866/PKU.WHXB201305152 shu

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

CHEN Zheng-Jun ¹ ,
JIANG Qing-Lin ² ,
HE Gu ^1,3, ,
HAN Bo ⁴ ,
GUO Li ¹

1.
1 West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China;
2 Department of Pharmacy, Chengdu Medical College, Chengdu 610500, P. R. China;
3 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
4 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China

Received Date: 11 March 2013
Available Online: 15 May 2013
Fund Project: 国家自然科学基金(30901837, 81001357, 81273471)资助项目 (30901837, 81001357, 81273471)

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.
- Aryl-sulfamide derivative,
- Pyruvate kinase,
- Pharmacophore,
- Comparative molecular field analysis,
- Comparative molecular similarity indices analysis
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