PIN1 protein small-molecule inhibitor and application thereof

A technology of small molecule compounds and uses, applied in the field of PIN1 protein small molecule inhibitors, can solve the problems of poor efficacy and cell permeability, and achieve the effect of improving survival rate and survival time, inhibiting proliferation and volume

Active Publication Date: 2021-06-22
XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the poor efficacy and cell permeability of these PIN1 inhibitors do not meet the requirements

Method used

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  • PIN1 protein small-molecule inhibitor and application thereof
  • PIN1 protein small-molecule inhibitor and application thereof
  • PIN1 protein small-molecule inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Example 1. The natural PIN1 small molecule inhibitor can be detected in the serum of tumor patients

[0072] Using GC-MS / MS technology, the serum of 10 patients with colorectal cancer was analyzed, and it was found that there were natural small molecule inhibitors of PIN1 in the serum of 9 / 10 patients

[0073] (Such as figure 1 A), therefore, it is used as a potential biomarker in this embodiment.

Embodiment 2

[0074] Example 2. PIN1 small molecule inhibitors inhibit the proliferation of colon cancer cell lines

[0075] CCK-8 reagent continuously detects the co-culture of human colon cancer cell lines DLD-1, HT-29 and mouse colon cancer cell line CT26 with different concentrations of PIN1 small molecule inhibitors, and found that the inhibitors have the ability to inhibit tumor cell proliferation, and Concentration gradient dependent (such as figure 1 shown in B-1D).

[0076] Continuous monitoring of tumor cell proliferation in vitro for 1-5 days revealed that tumor cell proliferation was inhibited after 5 days of high-concentration PIN1 small molecule inhibitor treatment (such as figure 2 shown in A).

Embodiment 3

[0077] Example 3. Small molecule inhibitors of PIN1 inhibit the migration ability of colon cancer cell lines

[0078] Using cell scratch experiments, it was found that the migration ability of tumor cells decreased after treatment with high concentrations of PIN1 small molecule inhibitors (such as figure 2 B), and reduced the sphere formation efficiency of tumor cells (as shown in figure 2 C shown).

[0079] Experiments have found that small molecule inhibitors of PIN1 have the same ability to inhibit the proliferation of tumor cell spheres after 3D culture of tumor cells (such as figure 2 D), indicating that it has good penetrability and can directly enter cells to play a role.

[0080] Live cells were labeled with green fluorescence by Calcein-AM, and dead cells were labeled with red fluorescence by SYTOX. The results were observed by laser scanning confocal microscopy. It can be seen that the number of viable cells was significantly reduced after treatment with high-co...

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Abstract

The invention provides a small molecule compound which is characterized in that the small molecule compound is a compound shown in the following structural formula or a stereoisomer, a geometric isomer, a tautomer, a racemate, a hydrate, a solvate, a metabolite, and a pharmacically acceptable salt or prodrug of the compound, the small molecule compound has at least one of the following applications: the small molecule compound is used for preparing a medicine serving as a peptidyl prolyl isomerase PIN1 inhibitor; the compound is used for preparing medicines for treating diseases related to PIN1 protein expression and dysfunction.

Description

technical field [0001] The present invention relates to an active small molecule compound, in particular to a PIN1 protein small molecule inhibitor and its application. Background technique [0002] With the improvement of human living standards and medical conditions, the global life expectancy has been greatly improved. However, due to environmental pollution, the prevalence of bad living and eating habits, and the aging population, the incidence of diseases such as cancer and Alzheimer's is increasing year by year. According to the forecast of the World Health Organization and the International Agency for Research on Cancer (IARC), the future global cancer incidence and mortality will increase from 18 million in 2018 to 29.5 million in 2040, with an increase rate of 63.4%. Cancer has become the second leading cause of death after cardiovascular disease. Chemotherapy drugs currently used to treat cancer are mainly cytotoxic drugs such as alkylating agents, cisplatin, met...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C49/603A61P35/00A61P35/04A61P29/00A61P25/00A61K31/122
CPCC07C49/603A61K31/122A61P35/00A61P35/04A61P29/00A61P25/00
Inventor 马妍慧沈立松
Owner XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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