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

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The specialised, focused library is developed on demand with the most recent virtual screening and parameter assessment technology, guided by the Receptor.AI drug discovery platform. This approach exceeds the capabilities of traditional methods and offers compounds with higher activity, selectivity, and safety.

From a virtual chemical space containing more than 60 billion molecules, we precisely choose certain compounds. Our collaborator, Reaxense, aids in their synthesis and provision.

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 utilise our cutting-edge, exclusive workflow to develop focused libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

It includes in-depth molecular simulations of both the catalytic and allosteric binding pockets, with ensemble virtual screening focusing on their conformational flexibility. For modulators, the process includes considering the structural shifts due to reaction intermediates to boost activity and selectivity.

Our library stands out due to several important features:

The Receptor.AI platform compiles comprehensive data on the target protein, encompassing previous experiments, literature, known ligands, structural details, and more, leading to a higher chance of selecting the most relevant compounds.
Advanced molecular simulations on the platform help pinpoint potential binding sites, making the compounds in our focused library ideal for finding allosteric inhibitors and targeting cryptic pockets.
Receptor.AI boasts over 50 tailor-made AI models, rigorously tested and proven in various drug discovery projects and research initiatives. They are crafted for efficacy, dependability, and precision, all of which are key in creating our focused libraries.
Beyond creating focused libraries, Receptor.AI offers comprehensive services and complete solutions throughout the preclinical drug discovery phase. Our success-based pricing model minimises risk and maximises the mutual benefits of the project's success.

partner

Reaxense

upacc

Q9UNE7

UPID:

CHIP_HUMAN

Alternative names:

Antigen NY-CO-7; CLL-associated antigen KW-8; Carboxy terminus of Hsp70-interacting protein; RING-type E3 ubiquitin transferase CHIP; STIP1 homology and U box-containing protein 1

Alternative UPACC:

Q9UNE7; A2IDB9; O60526; Q969U2; Q9HBT1

Background:

E3 ubiquitin-protein ligase CHIP, also known as Antigen NY-CO-7 and Carboxy terminus of Hsp70-interacting protein, plays a pivotal role in protein quality control. It targets misfolded chaperone substrates for proteasomal degradation, collaborates with ATXN3, and modulates the activity of several chaperone complexes. Its ability to ubiquitinate and regulate the stability and activity of various proteins underscores its significance in cellular homeostasis.

Therapeutic significance:

The involvement of E3 ubiquitin-protein ligase CHIP in Spinocerebellar ataxia, autosomal recessive, 16 (SCAR16), and Spinocerebellar ataxia 48 (SCA48) highlights its potential as a therapeutic target. Understanding the role of this protein could open doors to potential therapeutic strategies for these neurodegenerative diseases.