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.
