Azithromycin and roxithromycin derivatives as senolytic drugs

A derivative and pharmaceutical technology, applied in the field of anti-aging drugs, can solve problems such as failure

Pending Publication Date: 2021-07-23
LUNELLA BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In theory, such anti-aging drugs could have various undue effects associated with aging
However, drug development is a lengthy and expensive process that requires numerous clinical trials and is at risk of failure for one of many possible reasons

Method used

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  • Azithromycin and roxithromycin derivatives as senolytic drugs
  • Azithromycin and roxithromycin derivatives as senolytic drugs
  • Azithromycin and roxithromycin derivatives as senolytic drugs

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Embodiment Construction

[0034] The following description includes presently contemplated modes of carrying out exemplary embodiments of the method. The following description is not limiting, but merely illustrates the general principles of the invention.

[0035] As described herein, the method involves the development of screening assays for inducing senescence, and their use in identifying compounds with anti-aging activity, ie selectively inhibiting senescent cells and inducing senescent cell death. In some embodiments, the method can be used to identify and repurpose clinically approved therapeutics with anti-aging activity to treat aging and aging-related disorders. figure 1 Screening methodology according to the present method is shown. In step S101, normal fibroblasts are selected. Next, in step S102, the cells are exposed to a DNA damaging agent to induce senescence. For example, bromodeoxyuridine can be used as an injuring agent. In step S103, the senescent cells are treated with the can...

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PUM

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Abstract

This disclosure describes the use of azithromycin, roxithromycin, and telithromycin, including derivatives thereof, as senolytic drugs. BrdU was used to induce senescence in model human fibroblast cell lines. Also disclosed are methods for screening compounds for senolytic activity. The SRB assay was used to measure cell viability through protein content. Azithromycin roxithromycin, and telithromycin, clinically-approved pharmaceuticals, were found to be senolytic drugs. However, the closely-related parent compound, erythromycin, showed no senolytic activity. Azithromycin strongly induced both aerobic glycolysis and autophagy in human fibroblasts, but showed bi-phasic effects including on mitochondrial oxygen consumption rates with inhibitory activity at 50 muM and stimulatory activity at 100 muM. The xCELLigence real-time assay system showed that azithromycin preferentially targets senescent cells, removing approximately 97% (nearly a 25-fold reduction in senescent cells).

Description

technical field [0001] The present disclosure relates to senolytic drugs, a class of compounds that selectively induce the death of senescent cells. Background technique [0002] As diverse organisms undergo chronological aging, many genetic, phenotypic, and metabolic defects accumulate. This accumulation includes the onset of senescence in various cell types. The overall view of cumulative deficits is consistent with the "accumulated damage" hypothesis of aging. [0003] Aging is a clear sign of normal chronological aging. Initiation and induction of key lysosomal enzymes (β-galactoside enzyme) and lipofuscin (a known aging pigment), senescence involves a possibly irreversible cell cycle arrest. Interestingly, SASP leads to the secretion of a large number of inflammatory cytokines such as IL-1-β and IL-6, thereby allowing senescent cells to "contagiously" spread the senescent phenotype from one cell type to another through chronic inflammation. whole body. This chroni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7042A61K31/7048A61P31/04
CPCA61K31/7048A61K31/7052A61P39/00A61K31/65A61K2300/00A61K45/06A61P43/00
Inventor F·苏特加M·P·利桑蒂
Owner LUNELLA BIOTECH INC
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