Slowing intervertebral disc aging in mice through long-term systemic treatment with the senolytic BCL-2/BCL-xL proteolysis targeting chimera (PROTAC) 753b (IMAGE)
Caption
Figure 1. Schematic of study design. (A) PROTAC 753b consists of a BCL-xL/2 binding moiety connected to a Von Hippel-Lindau (VHL) E3 ligase ligand via a linker. 753b functions by binding to BCL-XL/BCL-2, targeting them both to the VHL E3 ligase for ubiquitination and subsequent proteasomal degradation. Treatment of mice (B) with 753b via IP injection through a treatment regimen (C) consisted of 6 1-month treatment cycles comprised of a 2-week drug delivery period followed by a 2-week rest period. During the treatment period, the drug was delivered 2 times per week. Peritoneal injections of 753b (5 mg/kg) or vehicle control (10% ethanol, 30% PEG 400 and 60% PHOSAL 50 PG) began at 16 months of age (16M) ending at 22 months of age (22 M) for a total of 6 months. Vehicle (10% ethanol, 30% PEG 400 and 60% PHOSAL 50 PG), 753b (5mg/kg 753b). (D) Outcome measures of harvested IVDs from the spines.
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Copyright: © 2026 Alexander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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