Focused On-demand Library for E3 ubiquitin-protein ligase CBL

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The focused library is created on demand with the latest virtual screening and parameter assessment technology, supported by the Receptor.AI drug discovery platform. This method is more effective than traditional methods and results in higher-quality compounds with better activity, selectivity, and safety.

The compounds are cherry-picked from the vast virtual chemical space of over 60B molecules. The synthesis and delivery of compounds is facilitated by our partner Reaxense.

Contained in the library are leading modulators, each labelled with 38 ADME-Tox and 32 physicochemical and drug-likeness qualities. In addition, each compound is illustrated with its optimal docking poses, affinity scores, and activity scores, giving a complete picture.

Our top-notch dedicated system is used to design specialised libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

It includes comprehensive molecular simulations of the catalytic and allosteric binding pockets and the ensemble virtual screening accounting for their conformational mobility. In the case of designing modulators, the structural changes induced by reaction intermediates are taken into account to leverage activity and selectivity.

Several key aspects differentiate our library:

Receptor.AI compiles an all-encompassing dataset on the target protein, including historical experiments, literature data, known ligands, and structural insights, maximising the chances of prioritising the most pertinent compounds.
The platform employs state-of-the-art molecular simulations to identify potential binding sites, ensuring the focused library is primed for discovering allosteric inhibitors and binders of concealed pockets.
Over 50 customisable AI models, thoroughly evaluated in various drug discovery endeavours and research projects, make Receptor.AI both efficient and accurate. This technology is integral to the development of our focused libraries.
In addition to generating focused libraries, Receptor.AI offers a full range of services and solutions for every step of preclinical drug discovery, with a pricing model based on success, thereby reducing risk and promoting joint project success.

partner

Reaxense

upacc

P22681

UPID:

CBL_HUMAN

Alternative names:

Casitas B-lineage lymphoma proto-oncogene; Proto-oncogene c-Cbl; RING finger protein 55; RING-type E3 ubiquitin transferase CBL; Signal transduction protein CBL

Alternative UPACC:

P22681; A3KMP8

Background:

E3 ubiquitin-protein ligase CBL, also known as Casitas B-lineage lymphoma proto-oncogene, plays a pivotal role in cellular signaling. It functions as a negative regulator by mediating ubiquitination and subsequent degradation of various cell surface receptors, including EGFR and receptor tyrosine kinases. This process is crucial for terminating signaling pathways to maintain cellular homeostasis. CBL's involvement in osteoblast differentiation and apoptosis highlights its significance in bone metabolism.

Therapeutic significance:

CBL's mutation is linked to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, showcasing its clinical relevance. Understanding the role of E3 ubiquitin-protein ligase CBL could open doors to potential therapeutic strategies, especially in malignancies and bone disorders. Targeting CBL's activity or its pathways could offer novel approaches for treating related diseases.