Focused On-demand Library for E3 ubiquitin-protein ligase TRIM23

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.

We carefully select specific compounds from a vast collection of over 60 billion molecules in virtual chemical space. Our partner Reaxense helps in synthesizing and delivering these compounds.

The library includes a list of the most effective modulators, each annotated with 38 ADME-Tox and 32 physicochemical and drug-likeness parameters. Furthermore, each compound is shown with its optimal docking poses, affinity scores, and activity scores, offering a detailed summary.

We use our state-of-the-art dedicated workflow for designing focused 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

P36406

UPID:

TRI23_HUMAN

Alternative names:

ADP-ribosylation factor domain-containing protein 1; GTP-binding protein ARD-1; RING finger protein 46; RING-type E3 ubiquitin transferase TRIM23; Tripartite motif-containing protein 23

Alternative UPACC:

P36406; Q9BZY4; Q9BZY5

Background:

E3 ubiquitin-protein ligase TRIM23, known for its roles in autophagy activation during viral infection, is pivotal in cellular defense mechanisms. It activates TANK-binding kinase 1 (TBK1), facilitating the phosphorylation of the selective autophagy receptor SQSTM1. TRIM23's auto-ubiquitination of its ADP-ribosylation factor (ARF) domain enhances its GTPase activity, crucial for autophagosome recruitment. Additionally, in the context of microbial infection, TRIM23 mediates TRAF6 auto-ubiquitination in response to human cytomegalovirus protein UL144, modulating NF-kappa-B activation.

Therapeutic significance:

Understanding the role of E3 ubiquitin-protein ligase TRIM23 could open doors to potential therapeutic strategies.