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NLRP3 inhibitor

A technology of inhibitors and preparations, applied in the field of small molecule drugs, which can solve the problems of unknown effect and retention of small molecules

Pending Publication Date: 2022-05-31
SHANGHAI EAST HOSPITAL EAST HOSPITAL TONGJI UNIV SCHOOL OF MEDICINE
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some small-molecule inhibitors of NLRP3 have been reported, they are still in basic research or clinical phase 1 / 2 research, and no drugs have been used clinically, and the effects of these small molecules are also unknown

Method used

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Embodiment 1

[0020] The experimental methods in the following implementation cases are conventional experimental methods unless otherwise specified. Unless otherwise specified, the reagents and consumables used in the experiment were from mainstream suppliers in this research field, such as Sigma, Invivogene, R&D, Corning, and Biolegend.

[0021] 1. Acquisition of mouse bone marrow-derived macrophages (BMDMs)

[0022] Bone marrow cells were extracted from mice aged 6-8 weeks, cultured in M-CSF medium containing 10 ng / ml for 7 days, and half of the fresh medium was added on the fourth day to obtain BMDMs. BMDMs were collected and replanted in cell culture plates (1*10 6 / ml) overnight, proceed to the next stage of the experiment.

[0023] 2. Activation of the inflammasome

[0024] (1) Activation of NLRP3 inflammasome: BMDMs were pretreated with LPS for three hours, then the original culture medium was replaced with serum-free medium, and different concentrations of UK5099 were added for ...

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Abstract

The invention relates to an NLRP3 inhibitor. The effective component of the inhibitor is a small molecule compound UK5099. In-vivo and in-vitro experiments prove that UK5099 can specifically inhibit NLRP3 inflammasome activation, and a new method is provided for clinical treatment of NLRP3 related diseases.

Description

technical field [0001] The invention belongs to the field of small molecule drugs, in particular to an NLRP3 inhibitor. Background technique [0002] The NLRP3 inflammasome is a protein complex composed of three parts: the sensor molecule NLRP3, the adapter protein ASC and the effector protein precursor procaspase-1, which can sense various danger signals in the body and be activated, and then cut the cytokine IL -1β and IL-18, as well as the porin gasdermin D, promote inflammatory responses and induce apoptosis. Since its discovery in 2002, a large number of studies have shown that the NLPR3 inflammasome is closely related to Alzheimer's disease, Parkinson's disease, atherosclerosis, gout, rheumatic diseases, infectious diseases, asthma and other diseases. Therefore, the development of drugs that can specifically inhibit NLRP3 is expected to provide new means for the treatment of these diseases, and it is also the focus of competition among major pharmaceutical companies a...

Claims

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Application Information

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IPC IPC(8): A61K31/405A61P25/28A61P9/10A61P19/06A61P29/00A61P31/00A61P11/06A61P43/00
CPCA61K31/405A61P25/28A61P9/10A61P19/06A61P29/00A61P31/00A61P11/06A61P43/00Y02A50/30
Inventor 王飞龙
Owner SHANGHAI EAST HOSPITAL EAST HOSPITAL TONGJI UNIV SCHOOL OF MEDICINE
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