Small-molecule inhibitor for targeted inhibition of PITPNM3 and application of small-molecule inhibitor

A small-molecule inhibitor and targeted technology, applied in the direction of organic active ingredients, active ingredients of heterocyclic compounds, medical preparations containing active ingredients, etc., can solve cancer metastasis, poor clinical prognosis, and clinical treatment failure of breast cancer patients and other issues, to achieve the effect of a wide range of applications

Active Publication Date: 2022-03-04
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the diagnosis and treatment methods for breast cancer have made great progress, some breast cancer patients still have cancer metastasis, and breast cancer distant metastasis is one of the most important reasons for poor clinical prognosis and clinical treatment failure

Method used

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  • Small-molecule inhibitor for targeted inhibition of PITPNM3 and application of small-molecule inhibitor
  • Small-molecule inhibitor for targeted inhibition of PITPNM3 and application of small-molecule inhibitor
  • Small-molecule inhibitor for targeted inhibition of PITPNM3 and application of small-molecule inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1PI

[0038] Example 1 PITPNM3 key domain modeling and small molecule docking

[0039] The molecular size of PITPNM3 protein is about 108KD, with a total length of 980 amino acids. It is a transmembrane receptor, mainly including an N-terminal calcium ion binding domain (acidic calcium-binding domian) and a C-terminal PYK2-binding domian (PYK2-binding domian). The amino acid sequence of the C-terminal key domain (C-terminal PYK2 binding domain) protein of PITPNM3 is shown in SEQ ID NO.1. Based on the research on PITPNM3 (Lev S, Hernandez J, Martinez R, ChenA, Plowman G, & Schlessinger, J. Identification of a novel family of targets of pyk2 related to drosophila retinal degeneration b(rdgb) protein. Molecular & Cellular Biology, 19(3) , 2278.), the C-terminal PYK2-binding domain of PITPNM3 is mainly responsible for the binding to PYK2 and the phosphorylation of PYK2. When CCL18 binds to PITPNM3, the activated PITPNM3 can phosphorylate PYK2 through the C-terminal PYK2-binding domain ...

Embodiment 2

[0045] Example 2 Screening of Small Molecule Inhibitors Targeted to Inhibit PITPNM3

[0046] Through the following activity test, toxicity test and tumor cell migration inhibition test, the 100 kinds of small molecule inhibitors initially screened in Example 1 were gradually screened in order to screen out those with high activity, low toxicity and better inhibition of tumor cell migration. Small molecule inhibitors targeting PITPNM3.

[0047] (1) Screening of 100 small molecule inhibitors based on cytotoxicity test

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PUM

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Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to a small-molecule inhibitor for targeted inhibition of PITPNM3 and application of the small-molecule inhibitor. According to the invention, 11 small molecule inhibitors for targeted inhibition of PITPNM3, which have a biological effect of targeted inhibition of PITPNM3 mediated cell adhesion and a biological effect of targeted inhibition of CCL18-PITPNM3 mediated cell migration adhesion, are screened by virtue of computer-aided drug design and high-throughput drugs, and can inhibit various PITPNM3 activated and mediated tumor metastasis; the compound has the advantages of wide application range and high targeting property, such as breast cancer, hepatocellular carcinoma, pancreatic ductal carcinoma and lung cancer.

Description

technical field [0001] The invention belongs to the technical field of bioengineering and biomedicine, and in particular relates to a small molecule inhibitor targeting PITPNM3 and its application. Background technique [0002] Breast cancer is the malignant tumor with the highest incidence rate in women in my country, and breast cancer metastasis is the main cause of death in breast cancer patients. Although the diagnosis and treatment methods for breast cancer have made great progress, some breast cancer patients still have cancer metastasis, and distant metastasis of breast cancer is one of the most important reasons for poor clinical prognosis and clinical treatment failure. Like the distant metastasis of other malignant tumors, its distant metastasis is closely related to the tumor microenvironment. In the malignant tumor microenvironment, various immune cells will infiltrate and produce various inflammatory factors, and these inflammatory factors communicate with the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/497A61K31/5377A61K31/519A61K31/4196A61K31/196A61K31/365A61K31/505A61K31/37A61K31/423A61K31/422A61P35/04
CPCA61K45/00A61K31/497A61K31/5377A61K31/519A61K31/4196A61K31/196A61K31/365A61K31/505A61K31/37A61K31/423A61K31/422A61P35/04
Inventor 宋尔卫龚畅姜文国刘子豪
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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