The Approach
Harnessing the body’s own biology to create therapies for disease
Generian’s discovery platform harnesses E3 ligase biology to enhance the activation of beneficial cellular pathways. Generian uses a fine-tuned approach that selectively targets a protein in its active form without overriding important cellular control mechanisms. Our medicines increase specific target protein activity and improve cellular function and healthspan by restoring the body’s natural biological networks while maintaining physiological cues required for homeostasis.
Built on Biology
As our bodies age, our cells no longer function as they should. The activity of naturally protective signaling networks decreases, impacting cells’ ability to sense and respond to disturbances in nutrient levels, exert quality control, regulate gene expression, modify protein activity and perform key biological functions. This contributes to the development of a number of chronic diseases all associated with a substantial burden including cardiovascular disease, cancer, and neurodegeneration.
The Role of E3 Ligases
E3 ligases are a powerful tool to modulate protein activity. Though they can be harnessed to degrade harmful proteins, they can also be used to increase the activity of beneficial proteins that play critical roles in protective signaling networks, improving cellular function.
The Generian drug discovery engine enables rapid and scalable target discovery through the use of proprietary tools and assays that pinpoint relevant target proteins, identify specific E3 ligases and develop small molecule therapeutic candidates. Generian’s approach expands the playbook of druggable targets, including transcription factors.
Generian’s therapies are designed to inhibit specific E3 ligases, thereby preventing the degradation of beneficial target proteins to enhance cellular response and exert a beneficial effect.
Discovery Process
There are more than 600 E3 ligases in the human body, which are widely thought to serve unique functions. Much like protein kinases and their corresponding substrates, E3 ligases and their respective substrates are believed to be biologically linked and work together in a coordinated network.
Generian’s state-of-the-art systematic and unbiased approach identifies the most target-relevant E3 ligases using a novel high-throughput screening platform. We have applied this often underappreciated strategy to develop a proprietary screening assay that is used to analyze millions of small molecules for their ability to block the specific interaction between the E3 ligase substrate binding domain and the target protein, preventing the target protein from being degraded. Generian’s approach validates drug targets through integrated preclinical pharmacology and biomarker analyses.
