Method for screening small-molecule inhibitors by taking cathepsin D as target point

Abstract

The invention belongs to the technical field of medical chemistry, and relates to a drug screening method, in particular to a method for establishing a virtual screening model and an in vitro testing model of small-molecule inhibitors by taking cathepsin D as a target point. The method comprises the following steps: (1) acquiring, analyzing and processing a three-dimensional structure of cathepsin D protein; (2) establishing and processing a small-molecule database; (3) establishing a computer virtual screening system; (4) applying the computer virtual screening system obtained in the step (3) to screen a small-molecule ligand library obtained in the step (2); (5) predicting absorption, distribution, metabolism, excretion and toxicity (ADME-T). After the method for screening the cathepsin D inhibitors is adopted, six seedling compounds having cathepsin D inhibition activity are finally screened out; the method has the advantages of being rapid, economical and efficient, greatly increases the efficiency and provides a basis for finding the cathepsin D small-molecule inhibitors. The compounds, which are obtained by using the method and have the cathepsin D inhibition activity, can be further used for developing novel anti-cancer drugs.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and relates to a drug screening method, in particular to a drug screening method using virtual screening technology combined with in vitro biological activity evaluation, in particular to a virtual screening model and an in vitro method for small molecule inhibitors targeting cathepsin D. The method for establishing the test model, and the compound with cathepsin D inhibitory activity obtained by applying the method can be further used in the development of new anticancer drugs. Background technique [0002] Data show that malignant tumors have become a major disease threatening human beings. Tumor chemotherapy is still the main means of treating malignant tumors. Due to the disadvantages of chemical drugs, such as high toxicity, poor selectivity, and easy drug resistance, their clinical application has begun to be limited. Therefore, the development of anti-tumor drugs with good sel...

AI Technical Summary

Problems solved by technology

[0008] In view of the defects of high cost, long period, and low success rate in traditional drug screening methods, in recent years, with the development of computer simulation and computational chemistry, the use of simulation technology for drug screening has become a reality; therefore, the inventors of the present application Based on molecular docking technology, virtual screening of cathepsin D targets is proposed, and a screening method for small molecule inhibitors targeting cathepsin D is provided.

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