Studies on the pIC50 of 4,5-Diarylisoxazole as HSP90 Inhibitors

Author(s): Jing Ouyang, Xiaoqian Liu, Yutao Zhao, Ying Liu, Hongzong Si*, Honglin Zhai

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 4 , 2020

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Abstract:

Background: Heat Shock Protein 90(HSP90) inhibitors are involved in multiple anticancer pathways, which indicate many important novel molecular targets for cancer therapy. However, the characteristics of poor water solubility, liver toxicity and finite bioavailability of the present inhibitors limit clinical application. Hence, it is crucial to evaluate the characteristics of compounds and develop new drugs with hypotoxicity and high-bioactivity.

Methods: Quantitative Structure-Activity Relationship (QSAR) has been an effective method for screening novel structures and predicting various properties of the synthesized compounds. Heuristic Method (HM) and Gene Expression Programming (GEP) algorithm were used to establish linear and nonlinear models severally.

Results: The results showed that HM has good correlation coefficients of R2 and lower S2 as 0.79 and 0.29 for the training set and GEP has better values of 0.89 and 0.05, respectively.

Conclusion: Both models have the capability of prediction but the nonlinear model developed by GEP has a more excellent predictive ability and indicates further optimization of the HSP90 inhibitors.

Keywords: HSP90 inhibitors, pIC50, quantitative structure-activity relationship, model, gene expression programming, Heuristic Method.

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VOLUME: 17
ISSUE: 4
Year: 2020
Page: [467 - 478]
Pages: 12
DOI: 10.2174/1570180816666190329221959
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