E3 Ligases Research Platform

Central to targeted protein degradation (TPD) are E3 ubiquitin ligases, enzymes that tag target proteins with ubiquitin for degradation by the proteasome. Despite the human genome encoding over 600 E3 ligases, only a small fraction, including well-known representatives like CRBN and VHL, are currently exploited in TPD drug development. This delineates the vast, untapped potential that remains in harnessing these crucial enzymes. At the forefront of this exploration, we have developed a cutting-edge research platform designed to harness this potential fully. Our E3 ligases research platform is dedicated to discovering novel E3 ligases that can be leveraged for therapeutic interventions, particularly for diseases where traditional drug modalities have failed. Moreover, the platform also accelerates the design of effective binders that demonstrate ideal outcomes within a condensed timeline.

Our E3 Ligases Research Platform

Our E3 ligases research platform is a state-of-the-art framework built on cutting-edge technologies and deep domain expertise. This platform is designed to accelerate the discovery and application of E3 ligases in TPD.

The platform focuses on:

• Identification of Novel E3 Ligases: Utilizing genomic and proteomic analyses, we systematically screen for E3 ligases that demonstrate unique interactions with specific disease processes. This facet of our platform is crucial for expanding the known repertoire of ligases that can be targeted with TPD strategies.
• Designing Effective Binders: Once potential ligases are identified, our platform facilitates the swift design of effective molecular binders. These binders are critical in mediating the interaction between the E3 ligases and the target proteins, ensuring targeted and efficient degradation.

To achieve these objectives, our research strategy consists of the following steps:

• Selection of E3 Ligase: Based on their potential therapeutic relevance and disease association, we meticulously choose E3 ligases or develop novel E3 ligases by employing state-of-the-art screening methodologies. This step ensures that we target ligases with the highest likelihood of successful application in TPD.
• Rigorous Evaluation of E3 Ligase Activity: Following selection, we engage in a thorough evaluation of the activity levels of the chosen E3 ligases. This evaluation is conducted via in vitro and in vivo studies. This step is critical for understanding their functional roles and designing strategies to harness their degradation capabilities effectively.
• Discovering Hits through Affinity-Based Screening: By employing advanced techniques like DNA-encoded libraries (DEL) and surface plasmon resonance (SPR), we systematically identify compounds (binders) with strong binding affinities to E3 ligases, known as hits.
• Comprehensive Hit Validation: Once hits are identified, we conduct rigorous validation processes to confirm their efficacy and binding strength, ensuring only the most promising candidates move forward.
• Degradation Validation: To confirm efficacy, we validate protein degradation across various cell types using cutting-edge techniques.
• In-depth Mechanistic Studies: Next, our research emphasizes understanding the molecular mechanisms underlying E3 ligase function and target protein degradation. Mechanism-driven insights guide rational optimization strategies of binders.
• Strategic Decision-Making for R&D: In final stage, decisions are made regarding the progression of compounds based on potency, safety, efficacy in animal models, and applicability across broad target protein classes, ensuring that only the most promising candidates advance through the pipeline.

Our Advantages

• Comprehensive Expertise: Our team comprises leading scientists in structural biology, medicinal chemistry, and computational biology, ensuring a multidisciplinary approach to E3 ligase research.
• Proprietary Technology: We have developed proprietary tools and technologies for ligand design and E3 ligase identification, providing a competitive edge in the rapidly evolving TPD landscape.
• Robust Collaboration Network: Our platform benefits from strategic partnerships with academic institutions, biotech companies, and pharmaceutical leaders, fostering knowledge exchange and accelerating innovation.
• Focus on Patient-Centric Outcomes: By targeting previously untapped E3 ligases, we aim to develop therapies that address unmet medical needs, offering hope to patients with challenging diseases.

The vast and largely unexplored repertoire of human E3 ligases holds tremendous potential for transforming TPD drug development. Our E3 ligases research platform is dedicated to unlocking this potential by systematically identifying novel ligases, designing effective binders, and implementing innovative strategies to overcome existing challenges. For more information, please feel free to contact us.

It should be noted that our service is only used for research, not for clinical use.