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MTOR inhibitor and application thereof

A technology of inhibitors and proteins, applied in the direction of anti-virus agents, DNA/RNA fragments, medical preparations containing active ingredients, etc., can solve problems that have not yet been developed, and achieve a wide range of medicinal prospects and high specificity

Active Publication Date: 2022-06-14
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the drug strategy of using protein to inhibit mTOR to treat tumors has not yet been developed.

Method used

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  • MTOR inhibitor and application thereof
  • MTOR inhibitor and application thereof
  • MTOR inhibitor and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0040] Example 1. A method for screening mTOR inhibitors

[0041] A method for screening mTOR inhibitors, comprising the steps of:

[0042] 1) Construct the fusion expression vector (HAFlag-xxID-Rheb) of biotin ligase (xxID) and Rheb, transfer the vector into HeLa cells, screen the HeLa-xxID-Rheb stable expression cell line, and construct the control cell line HeLa- xxID stably expressing cell lines were cultured in a medium containing 10% dialysis serum; 16 hours before the experiment, a serum-free medium was used to avoid the interference of insulin.

[0043]2) Then add insulin (0.9μM) and biotin (50μM) to the HeLa-xxID-Rheb stable expression cell line for stimulation, stimulate for 15min, add biotin (50μM) to the HeLa-xxID stable expression cell line to stimulate, without Add insulin, stimulate for 15min, lyse the sample, extract the protein, pull down with streptavidin, enrich the biotinylated protein, perform reductive alkylation on streptavidin magnetic beads, trypsin d...

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Abstract

The invention relates to the technical field of biology, in particular to an mTOR inhibitor and application thereof. The mTOR inhibitor is obtained by mutating the 14th, 17th and 18th aspartic acids in 30 amino acids at the C terminal of ATP6AP1 protein into alanine, and the sequences of the 30 amino acids are as shown in SEQ ID NO: 1. A novel proximity marker technology screening method is utilized to find a C-terminal fragment (C tail) of ATP6AP1 protein, the C-terminal fragment (C tail) is used as a guanylate exchange factor (GEF) of Rhb and can activate Rhb, on the basis, aspartic acid at the 14th site, the 17th site and the 18th site in 30 amino acids at the C terminal is mutated into alanine, a new mTOR inhibitor is obtained, and the mTOR inhibitor can be combined with and block inhibition of endogenous ATP6AP1 on Rhb so as to inhibit an mTORC1 signal channel.

Description

technical field [0001] The present invention relates to the field of biotechnology, in particular to an mTOR inhibitor and application thereof. Background technique [0002] mTOR (mechanistic mammalian target of rapamycin) is a kind of protein kinase involved in intracellular signal transmission in mammals and other animals. It plays an important role in protein translation, autophagy, immune regulation, cytoskeleton regulation, gene transcription, etc. It is closely related to basic life phenomena such as cell growth, division and death. mTOR is a protein known to be discovered as an intracellular target of rapamycin that exhibits potent immunosuppressive and anticancer effects, and is a giant serine-threonine kinase with a molecular weight of 290,000. [0003] At present, mTOR inhibitors have been widely studied, but as chemotherapeutic drugs, their application has different defects. The development of mTOR inhibitors can be roughly divided into three stages, the first b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C12N9/12C12N15/85C12N15/62C12Q1/02G01N33/68A61K38/17A61P35/00A61P39/06
CPCC07K14/4703C12N9/1205C12N15/85C12N9/14G01N33/5005G01N33/6848C12Y306/05002C12Y207/1101C12Y207/1102A61K38/1709A61P39/06A61P35/00C12N2800/107C07K2319/00Y02A50/30
Inventor 松阳洲冯然刘峰吴苏周志芬李若菲
Owner SUN YAT SEN UNIV