TECHNOLOGY - Proteologics E3 Ligase Discovery Platform

Target Discovery
The ubiquitin system is implicated in numerous devastating diseases caused by viruses, malignant cell replication, neurdegeneration and others. Key regulators of protein ubiquitination are E3-ubiquitin ligases, a family of hundreds of enzymes that select proteins for ubiquitination and subsequent recycling or degradation. Proteologics utilizes its drug discovery capabilities to identify specific E3 ligases that present a rational for therapeutic target intervention. The target and drug discovery platform integrates in-depth biological knowledge of the ubiquitin system, proprietary protein informatics algorithms and state of the art wet-lab discovery and validation technologies.

E3 ligase - based Assay Development
Proteologics develops proprietary E3 ligase high throughput-screening (HTS) assays. In the course of developing its leading E3 anti-viral target, hPOSH, Proteologics has established a series of highly sensitive assays, which were adapted to an HTS format for the screening of chemical libraries for E3 inhibitors. The assays include: measurement of E3 self-ubiquitination, E3-substrate binding and E3-mediated substrate ubiquitination activities.

Substrate Identification
Proteologics employs several methods for the identification of E3's ubiquitination substrates. Proteologics considers that E3 activity assays based on substrate ubiquitination and binding significantly improve the likelihood of identifying authentic E3-based drugs. Therefore, Proteologics continuously develops supporting technologies for the identification of E3-interacting substrates.

Drug Discovery
Screening of chemical libraries and hit identification is followed by a series of proprietary filtering activity assays intended to exclude irrelevant hits and isolate E3-specific inhibitors. Drug discovery, as well as all research activities at Proteologics, is supported by in-house-developed information data analysis and management systems.

Intellectual Property
Proteologics has a growing intellectual property portfolio to protect our E3 ligase targets and innovative technologies for establishing HTS-compatible target activity assays.