Citation: Cao Hongyu, Wu Yanhua, Ren Cong, Zhou Xingzhi, Jiang Ge. 3D-QSAR Studies on Biaryl-Type Inhibitors for the Bromodomains of CBP/P300[J]. Chemistry, ;2018, 81(6): 548-554. shu

3D-QSAR Studies on Biaryl-Type Inhibitors for the Bromodomains of CBP/P300

College of Life Science and Technology, Dalian University, Dalian 116622

Corresponding author: Jiang Ge, jiangge1004@163.com
Received Date: 16 January 2018
Accepted Date: 3 March 2018

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CREB-binding protein (CBP) and the highly homologous P300 are two subtypes of histone acetylase, which can bind to chromatin through their bromodomain (BRD). The CBP/P300 have already become a hot topic in the field of cancer target for they play important roles in the occurrence and development of tumors. In this study, the three-dimensional quantitative structure-activity relationship (3D-QSAR) was established based on the biaryl inhibitors for the bromodomain of CBP/P300. In order to determine the quantitative relationship between molecular structure and biological activity of biaryl inhibitors, the 3D-QSAR models of 35 inhibitors were established with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The predicted pIC₅₀ values of CoMFA and CoMSIA models were basically consistent with the actual pIC₅₀ values, indicating that both models had highly predictive ability and statistical significance. Information of steric, electrostatic, hydrophobic, hydrogen bond acceptor and donor fields provided by CoMFA and CoMSIA could propose novel drug design ideas to design more effective inhibitors with higher activity for the bromodomain of CBP/P300.
- Bromodomains of CBP/P300,
- Biaryl-type inhibitors,
- 3D-QSAR,
- CoMFA,
- CoMSIA
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