Focused On-demand Library for 11-beta-hydroxysteroid dehydrogenase type 2

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

This comprehensive focused library is produced on demand with state-of-the-art virtual screening and parameter assessment technology driven by Receptor.AI drug discovery platform. This approach outperforms traditional methods and provides higher-quality compounds with superior 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 utilise our cutting-edge, exclusive workflow to develop focused libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

It includes comprehensive molecular simulations of the catalytic and allosteric binding pockets and the ensemble virtual screening accounting for their conformational mobility. In the case of designing modulators, the structural changes induced by reaction intermediates are taken into account to leverage 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

P80365

UPID:

DHI2_HUMAN

Alternative names:

11-beta-hydroxysteroid dehydrogenase type II; Corticosteroid 11-beta-dehydrogenase isozyme 2; NAD-dependent 11-beta-hydroxysteroid dehydrogenase; Short chain dehydrogenase/reductase family 9C member 3

Alternative UPACC:

P80365; A7LB28; C5HTY7; Q13194; Q6P2G9; Q8N439; Q96QN8; Q99887; Q9UC50; Q9UC51; Q9UCW5; Q9UCW6; Q9UCW7; Q9UCW8

Background:

11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a pivotal role in converting active 11β-hydroxysteroids, like cortisol, into their inactive forms, such as cortisone. This enzymatic activity is crucial for maintaining glucocorticoid balance and protecting the mineralocorticoid receptor from glucocorticoid occupation. The protein is also involved in the metabolism of androgens and cholesterol derivatives, impacting immune cell migration and fetal development.

Therapeutic significance:

The dysfunction of 11β-HSD2 is directly linked to Apparent Mineralocorticoid Excess (AME), a condition characterized by severe hypertension and electrolyte imbalances from early life. Understanding the role of 11β-HSD2 could open doors to potential therapeutic strategies for AME and related disorders, offering hope for targeted treatments.