Protein Degrader

What is Protein Degrader?

Protein degrader is a chemical molecule that harnesses the intracellular protein degradation system to achieve targeted protein degradation, serving as both a powerful research tool and an emerging therapeutic strategy.

Molecular Structure

Protein Degrader is a heterobifunctional molecule composed of three core components: (1) a ligand that specifically binds the target protein (TP); (2) a ligand that recruits an E3 ubiquitin ligase; and (3) a chemical linker that connects these two ligands.

Working Principle and Mechanism

Fig1. Overview steps of entire target protein degradation by protein degraders [1].

Protein Degrader's mechanism of action is based on the cell's ubiquitin-proteasome system. Under physiological conditions, E3 ubiquitin ligases catalyze the polyubiquitination of specific substrate proteins. These tagged proteins are subsequently recognized and degraded by the proteasome, which constitutes the primary pathway for protein degradation in cells.

Protein Degrader molecules act as a bridge, simultaneously binding both the target protein and the E3 ligase, bringing them into nanometer proximity to form a "ternary complex." This proximity effect enables the E3 ligase to ubiquitinate the target protein, ultimately leading to its degradation by the proteasome. Importantly, the protein degrader molecule itself is not degraded during this process; instead, it dissociates from the target protein and enters the next catalytic cycle, giving it a recyclable nature.

Core Features of Protein Degrader

This mechanism confers unique advantages upon protein degraders: they represent a fast and reversible chemical knockdown strategy that operates through a catalytic cycle, enabling efficient degradation of target proteins at sub-stoichiometric concentrations. Compared to traditional small-molecule inhibitors, protein degraders directly eliminate disease-causing proteins rather than merely blocking their function, offering a new paradigm for studying disease-associated proteins and developing novel therapeutics.

Specifically, protein degrader technology demonstrates:

• High efficiency and low dosage: Catalytic mechanism enables sustained target degradation at low exposure levels
• Unlocking "undruggable" targets: Eliminates disease-causing proteins and modulates signaling pathways inaccessible to conventional therapies
• Complementary to genetic tools: Offers protein-level intervention that supplements nucleic acid-based knockdown/knockout approaches
• Biological fidelity: Faithfully mimics functional protein inactivation as seen in pharmacological settings

Clinical and Commercial Trajectory

This transformative modality has catalyzed intensive investment across academia and the biopharmaceutical sector. Our platform has supported the development of degraders targeting oncogenic drivers, immune checkpoints, viral capsid proteins, and neurodegenerative aggregates. protein degrader technology represents not merely an incremental improvement, but a fundamental redefinition of pharmacological intervention.

What We Offer?

Extended Degradation Technology Suite

Beyond conventional protein degraders, our platform pioneers four next-generation modalities to overcome biological limitations:

• Halo target protein degradation System: Engineered for inducible degradation of HaloTag® fusion proteins. Covalent chloroalkane tagging enables spatiotemporal control with tunable linker architectures—ideal for conditional knockdown studies and optogenetic integration.
• ATTEC (Autophagy-Tethering Compound): A ubiquitin-independent approach that directly engages LC3/GABARAP proteins within the autophagy machinery. This mechanism efficiently degrades protein aggregates, damaged organelles, and non-proteinaceous cargo via macroautophagy, expanding degradation capacity beyond proteasomal capacity.
• AUTAC (Autophagy-Targeting Chimera): Harnesses K63-linked polyubiquitination to tag cytoplasmic targets for selective autophagy. Particularly effective for degrading oligomeric proteins and condensates that resist conventional protein degrader-mediated proteasomal degradation.
• LYTAC (Lysosome-Targeting Chimera): Addresses the "extracellular proteome gap" by routing membrane and secreted proteins (e.g., growth factor receptors, cytokines) to lysosomal degradation via engagement of cell-surface receptors (CI-M6PR, ASGPR). Enables first-in-class targeting of oncogenic receptors and circulating pathogenic proteins.

Partnership Value Proposition & Engagement

Why Profacgen?

• De-risked Expertise: Extensive successful programs from hit identification to preclinical development, with deep expertise in "difficult" target classes
• True End-to-End Integration: Seamless workflow eliminates vendor handoffs—our medicinal chemists, biophysicists, and in vivo pharmacologists collaborate within a unified project team
• Global Resource Synthesis: Leveraging US and Asian research ecosystems for cost-effective, high-velocity execution

Next Steps

Contact our business development team for a confidential consultation. We deliver:

• Custom project scoping within 48 hours
• Detailed feasibility assessments and go/no-go criteria
• Transparent milestone-based pricing with FTE or fee-for-service flexibility

Profacgen is positioned as your strategically in pioneering targeted protein degradation therapeutics—transforming scientific vision into clinical reality.

Reference:

[1] Hongying Gao, Yu Rao. PROTAC Technology: Opportunities and Challenges. ACS Medicinal Chemistry Letters 2020 11 (3), 237-240. DOI: 10.1021/acsmedchemlett.9b00597