Targeted Protein Degradation

What we do

Present world where science is working towards personalized medicine, there is still much needed to be accomplished in the field of research and development.

B-Aatral Biosciences is a early stage Drug Discovery Company aims to contribute its share to the ever-growing need in betterment of healthcare system by investigating science behind some of less studied undruggable proteins by focusing on development of protein degradation drugs for cancer and other diseases.

Targeted Protein Degradation

We are specializing in Targeted Protein Degradation (TPD) and we utilize the PROTAC technology, to induce selective intracellular proteolysis. This process facilitates the removal of disease-causing proteins by the human body. We aim to create a drug discovery platform to enable small molecule degrading mechanisms to address various disorders. Our vision is to develop therapeutic through proprietary drug discovery pipelines. Our mission is to introduce and test novel small molecules for potential activity against cancer.

Ubiquitination

Ubiquitination is a post-translational modification of proteins that is necessary for a variety of cellular processes,including proteasome-mediated protein degradation, cell cycle progression, transcriptional regulation, DNA repair, and signal transduction. Ubiquitination necessitates the action of three enzymes in a specific order.

E1 (ubiquitin-activating enzyme), E2s (ubiquitin-conjugating enzymes), and E3 (ubiquitin ligase) are all involved in transferring ubiquitin to the target substrate to regulate the cellular function. E3 ligases are the largest class of enzymes proved to be the most ideal targets for therapeutic intervention.

PROTAC

The concept of induced protein degradation using PROTAC is a novel and promising therapeutic strategy currently revolutionizing drug discovery with its matchless benefits over the traditional modalities. PROTACs are heterobifunctional molecules employing a hit and run system with binding moieties for an E3 ubiquitin ligase and a protein of interest joined by a linker. The E3 ligase can initiate degradation by recruiting E2 enzyme loaded with ubiquitin to tag the surface of the target disease-causing protein which is subsequently recognized by the proteasome and degraded. Once the protein is degraded, PROTACs can continue catalyze another round of degradation. PROTAC technology holds immense potential to shift gears and reform the existing strategies to treat several diseases owing to the numerous advantages it has when compared with the existing small molecule inhibitors.

• Unlike the generally used small molecules, PROTACsare non-reliant on a stationary active site of target protein. This property enables the targeting of a significant percentage of proteins lacking enzymatic activity and expands the array of druggable proteome.
• High protein degradation efficiency can be achieved at nano molar concentrations with the use of PROTAC thereby reducing the possibilities for off target toxicity that generally occur as a result of high drug dosage. Additionally, PROTAC does not require high substrate affinity to bring about therapeutic effects as they catalytically tag the protein for degradation rather than blocking the protein activity.
• The target protein mutations and conformational changes rarely affect the mode of action of PROTAC and hence the chances for development of drug resistance as a consequence of mutation is significantly low.
• PROTAC very efficiently degrades the protein of interest and impede their overexpression and accumulation.