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P2026-based PROTAC
- Development stage
- Preclinical
- Lead developer
- Yale University
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intraarticular
01
Overview
P2026-based PROTAC is a preclinical-stage proteolysis-targeting chimera (PROTAC) designed to target and degrade the voltage-gated sodium channel Nav1.7 (SCN9A) [1029]. Developed by researchers at Yale University, the therapeutic utilizes a small-molecule binder, P2026, which targets the C-terminal domain of Nav1.7, linked to an E3 ubiquitin ligase-recruiting element to induce proteasomal degradation of the channel [1029]. Unlike traditional occupancy-based Nav1.7 inhibitors, which have faced clinical limitations due to poor selectivity and dose-limiting toxicities, this PROTAC achieves robust, dose-dependent degradation of full-length Nav1.7 in both neuronal cells and chondrocytes [1029]. It is being investigated for the treatment of osteoarthritis (OA) to simultaneously prevent cartilage degeneration and alleviate OA-associated pain [1029].
- Other names
- P2026-based PROTACP-2026-based PROTACP 2026-based PROTACP2026-based PROTACsP-2026-based PROTACsP 2026-based PROTACs
02
Targets
SCN9A (Sodium channel protein type 9 subunit alpha)
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