Редактирование: CRBN (раздел)

==Publications==

{{medline-entry
|title=Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32332723
|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.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Aniline Compounds
* Animals
* Blood Platelets
* Cell Line
* Cellular Senescence
* Female
* Humans
* Male
* Mice
* Mice, Transgenic
* Models, Animal
* Primary Cell Culture
* Proteolysis
* Sulfonamides
* Ubiquitin-Protein Ligases
* bcl-X Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181703
}}