Focused On-demand Library for Eukaryotic translation initiation factor 2-alpha kinase 1

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.

We carefully select specific compounds from a vast collection of over 60 billion molecules in virtual chemical space. Our partner Reaxense helps in synthesizing and delivering these compounds.

The library includes a list of the most effective modulators, each annotated with 38 ADME-Tox and 32 physicochemical and drug-likeness parameters. Furthermore, each compound is shown with its optimal docking poses, affinity scores, and activity scores, offering a detailed summary.

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.

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

Q9BQI3

UPID:

E2AK1_HUMAN

Alternative names:

Heme-controlled repressor; Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase; Heme-regulated inhibitor; Hemin-sensitive initiation factor 2-alpha kinase

Alternative UPACC:

Q9BQI3; A8K2R2; Q549K6; Q8NBW3; Q9HC02; Q9NYE0; Q9P0V6; Q9P1J5; Q9P2H8; Q9UHG4

Background:

Eukaryotic translation initiation factor 2-alpha kinase 1, known as Heme-regulated inhibitor, plays a pivotal role in metabolic-stress response by phosphorylating EIF2S1/eIF-2-alpha under stress conditions. This action halts global protein synthesis while selectively enabling ISR-specific mRNA translation, crucial for cellular adaptation to stress such as oxidative stress and heme deficiency.

Therapeutic significance:

Linked to Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome, understanding its function could unveil novel therapeutic avenues, especially in managing neurodevelopmental disorders where stress response pathways are implicated.