https://transhumanist.ru/index.php?action=history&feed=atom&title=CRBNCRBN - История изменений2026-04-20T11:14:17ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=CRBN&diff=6258&oldid=prevOdysseusBot: Новая страница: «Protein cereblon [AD-006] ==Publications== {{medline-entry |title=Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and impr...»2021-05-12T15:19:50Z<p>Новая страница: «Protein cereblon [AD-006] ==Publications== {{medline-entry |title=Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and impr...»</p>
<p><b>Новая страница</b></p><div>Protein cereblon [AD-006]<br />
<br />
==Publications==<br />
<br />
{{medline-entry<br />
|title=Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32332723<br />
|abstract=Small molecules that selectively kill senescent cells (SCs), termed senolytics, have the potential to prevent and treat various age-related diseases and extend healthspan. The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity. Here, we report the use of proteolysis-targeting chimera (PROTAC) technology to reduce the platelet toxicity of navitoclax (also known as ABT263), a Bcl-2 and Bcl-xl dual inhibitor, by converting it into PZ15227 (PZ), a Bcl-xl PROTAC, which targets Bcl-xl to the cereblon ([[CRBN]]) E3 ligase for degradation. Compared to ABT263, PZ is less toxic to platelets, but equally or slightly more potent against SCs because [[CRBN]] is poorly expressed in platelets. PZ effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia. With further improvement, Bcl-xl PROTACs have the potential to become safer and more potent senolytic agents than Bcl-xl inhibitors.<br />
|mesh-terms=* Adaptor Proteins, Signal Transducing<br />
* Aging<br />
* Aniline Compounds<br />
* Animals<br />
* Blood Platelets<br />
* Cell Line<br />
* Cellular Senescence<br />
* Female<br />
* Humans<br />
* Male<br />
* Mice<br />
* Mice, Transgenic<br />
* Models, Animal<br />
* Primary Cell Culture<br />
* Proteolysis<br />
* Sulfonamides<br />
* Ubiquitin-Protein Ligases<br />
* bcl-X Protein<br />
<br />
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181703<br />
}}</div>OdysseusBot