Focused On-demand Library for Exostosin-like 3

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.

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 use our state-of-the-art dedicated workflow for designing 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.

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

O43909

UPID:

EXTL3_HUMAN

Alternative names:

EXT-related protein 1; Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase; Hereditary multiple exostoses gene isolog; Multiple exostosis-like protein 3; Putative tumor suppressor protein EXTL3

Alternative UPACC:

O43909; D3DST8; O00225; Q53XT3

Background:

Exostosin-like 3, known as EXTL3, plays a pivotal role in the biosynthesis of heparan sulfate (HS), crucial for skeletal development and hematopoiesis. It initiates HS synthesis by transferring N-acetyl-alpha-D-glucosamine residues and is involved in postnatal pancreatic islet maturation and insulin secretion. EXTL3 also serves as a receptor for REG3A, REG3B, and REG3G, activating signaling pathways essential for keratinocyte proliferation, skin inflammation inhibition, and glucose tolerance.

Therapeutic significance:

EXTL3's involvement in immunoskeletal dysplasia with neurodevelopmental abnormalities highlights its potential as a therapeutic target. Understanding EXTL3's role could pave the way for innovative treatments for skeletal abnormalities, neurodevelopmental defects, and severe combined immunodeficiency.