Focused On-demand Library for E3 ubiquitin-protein ligase RNF138

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.

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.

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

Fig. 1. The sreening workflow of Receptor.AI

The method includes detailed molecular simulations of the catalytic and allosteric binding pockets, along with ensemble virtual screening that considers their conformational flexibility. In the design of modulators, structural changes induced by reaction intermediates are taken into account to enhance activity and selectivity.

Our library distinguishes itself through several key aspects:

The Receptor.AI platform integrates all available data about the target protein, including past experiments, literature data, known ligands, structural information and more. This consolidated approach maximises the probability of prioritising highly relevant compounds.
The platform uses sophisticated molecular simulations to identify possible binding sites so that the compounds in the focused library are suitable for discovering allosteric inhibitors and the binders for cryptic pockets.
The platform integrates over 50 highly customisable AI models, which are thoroughly tested and validated on a multitude of commercial drug discovery programs and research projects. It is designed to be efficient, reliable and accurate. All this power is utilised when producing the focused libraries.
In addition to producing the focused libraries, Receptor.AI provides services and end-to-end solutions at every stage of preclinical drug discovery. The pricing model is success-based, which reduces your risks and leverages the mutual benefits of the project's success.

partner

Reaxense

upacc

Q8WVD3

UPID:

RN138_HUMAN

Alternative names:

Nemo-like kinase-associated RING finger protein; RING finger protein 138; RING-type E3 ubiquitin transferase RNF138

Alternative UPACC:

Q8WVD3; B2RE17; Q9H8K2; Q9UF87; Q9UKI6

Background:

E3 ubiquitin-protein ligase RNF138 plays a pivotal role in DNA damage response, enhancing DNA resection and homologous recombination. It is recruited to double-strand breaks, promoting repair via homologous recombination and favoring this mechanism over non-homologous end joining by mediating ubiquitination of XRCC5/Ku80. Additionally, RNF138, in cooperation with UBE2Ds E2 ubiquitin ligases, facilitates homologous recombination through the ubiquitination of RBBP8/CtIP. It also participates in the ubiquitination and degradation of TCF/LEF with NLK and exhibits auto-ubiquitination activity with UBE2K.

Therapeutic significance:

Understanding the role of E3 ubiquitin-protein ligase RNF138 could open doors to potential therapeutic strategies.