Focused On-demand Library for E3 ubiquitin-protein ligase TRIM48

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

This extensive focused library is tailor-made using the latest virtual screening and parameter assessment technology, operated by the Receptor.AI drug discovery platform. This technique is more effective than traditional methods, offering compounds with improved 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.

In the library, a selection of top modulators is provided, each marked with 38 ADME-Tox and 32 parameters related to physicochemical properties and drug-likeness. Also, every compound comes with its best docking poses, affinity scores, and activity scores, providing a comprehensive overview.

We employ our advanced, specialised process to create targeted libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

The procedure entails thorough molecular simulations of the catalytic and allosteric binding pockets, accompanied by ensemble virtual screening that factors in their conformational flexibility. When developing modulators, the structural modifications brought about by reaction intermediates are factored in to optimize 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

Q8IWZ4

UPID:

TRI48_HUMAN

Alternative names:

RING finger protein 101; Tripartite motif-containing protein 48

Alternative UPACC:

Q8IWZ4; Q9BUW4

Background:

E3 ubiquitin-protein ligase TRIM48, also known as RING finger protein 101 and Tripartite motif-containing protein 48, plays a crucial role in cellular processes. It promotes K48-linked polyubiquitination of protein methyltransferase PRMT1, leading to its degradation. This action suppresses methylation of the PRMT1 substrate MAP3K5/ASK1, enhancing MAP3K5-dependent cell death under oxidative stress. Additionally, TRIM48-mediated ubiquitination of PRMT1 inhibits methylation of FOXO1, reducing FOXO1 transcriptional activity.

Therapeutic significance:

Understanding the role of E3 ubiquitin-protein ligase TRIM48 could open doors to potential therapeutic strategies.