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

A small molecule inhibitor, cathepsin technology, applied in special data processing applications, instruments, electrical digital data processing, etc., can solve the problems of low success rate, long cycle, high cost, etc., and achieve the effect of improving efficiency

Inactive Publication Date: 2017-11-14
FUDAN UNIV
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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 screenin

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

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Embodiment 1

[0065] To screen for small molecule inhibitors targeting cathepsin D, proceed as follows,

[0066] (1) Acquisition, analysis and processing of the three-dimensional structure of cathepsin D protein;

[0067] Search and obtain the three-dimensional structure of cathepsin D protein (PDB code: 1LYB) in the protein database (http: / / www.rcsb.org), which is a complex of cathepsin D protein and its inhibitor PepstatinA; use Schrödinger software Package maestro 10.1 (2015-01, version 10.1, http: / / www. com) Protein preparation wizard module to prepare, first hydrogenate the protein, and delete water molecules, α-mannose, β-mannose, N-acetyl-D-glucosamine in the protein, and then in the OPLS2005 force field conditions The energy optimization of the protein is carried out, and the RMSD of the heavy atoms in the final crystal structure is less than

[0068] (2) Construction and processing of small molecule ligand libraries for docking;

[0069] Obtain and filter out molecules with a...

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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...

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Application Information

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IPC IPC(8): G06F19/28A61K31/427A61K31/4439A61K31/415A61K31/4402A61K31/407
CPCA61K31/407A61K31/415A61K31/427A61K31/4402A61K31/4439G16B50/00
Inventor 张伟李英霞高顶顶包可婷
Owner FUDAN UNIV
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