Focused On-demand Library for Hepatocyte nuclear factor 4-alpha

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

Our detailed focused library is generated on demand with advanced virtual screening and parameter assessment technology powered by the Receptor.AI drug discovery platform. This method surpasses traditional approaches, delivering compounds of better quality with enhanced 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

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

P41235

UPID:

HNF4A_HUMAN

Alternative names:

Nuclear receptor subfamily 2 group A member 1; Transcription factor 14; Transcription factor HNF-4

Alternative UPACC:

P41235; A5JW41; B2RPP8; O00659; O00723; Q14540; Q5QPB8; Q6B4V5; Q6B4V6; Q6B4V7; Q92653; Q92654; Q92655; Q99864; Q9NQH0

Background:

Hepatocyte nuclear factor 4-alpha (HNF-4α), encoded by the gene with accession number P41235, serves as a pivotal transcriptional regulator. It orchestrates the expression of hepatic genes pivotal in the transition from endodermal cells to hepatic progenitors, thereby facilitating RNA polymerase II recruitment. Its roles extend to repressing CLOCK-BMAL1 activity, crucial for circadian rhythm in liver and colon cells.

Therapeutic significance:

HNF-4α is implicated in several metabolic disorders, including Maturity-onset diabetes of the young 1, Type 2 diabetes mellitus, and Fanconi renotubular syndrome 4. These associations underscore its potential as a therapeutic target, offering avenues for novel treatments in diabetes and metabolic syndrome management.