Focused On-demand Library for Eukaryotic translation initiation factor 2-alpha kinase 3

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.

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.

Our top-notch dedicated system is used to design specialised libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

This approach involves comprehensive molecular simulations of the catalytic and allosteric binding pockets and ensemble virtual screening that accounts for their conformational flexibility. In the case of designing modulators, the structural adjustments caused by reaction intermediates are considered to improve activity and selectivity.

Our library is unique due to several crucial aspects:

Receptor.AI compiles all relevant data on the target protein, such as past experimental results, literature findings, known ligands, and structural data, thereby enhancing the likelihood of focusing on the most significant compounds.
By utilizing advanced molecular simulations, the platform is adept at locating potential binding sites, rendering the compounds in the focused library well-suited for unearthing allosteric inhibitors and binders for hidden pockets.
The platform is supported by more than 50 highly specialized AI models, all of which have been rigorously tested and validated in diverse drug discovery and research programs. Its design emphasizes efficiency, reliability, and accuracy, crucial for producing focused libraries.
Receptor.AI extends beyond just creating focused libraries; it offers a complete spectrum of services and solutions during the preclinical drug discovery phase, with a success-dependent pricing strategy that reduces risk and fosters shared success in the project.

partner

Reaxense

upacc

Q9NZJ5

UPID:

E2AK3_HUMAN

Alternative names:

PRKR-like endoplasmic reticulum kinase; Pancreatic eIF2-alpha kinase

Alternative UPACC:

Q9NZJ5; A0AVH1; A0AVH2; B2RCU9; O95846; Q53QY0; Q53SB1

Background:

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as PRKR-like endoplasmic reticulum kinase and Pancreatic eIF2-alpha kinase, plays a pivotal role in metabolic-stress sensing. It phosphorylates EIF2S1/eIF-2-alpha under stress conditions, initiating the integrated stress response (ISR) for adaptation to challenges such as unfolded protein response (UPR) and low amino acid availability. This kinase is a key activator in global protein synthesis inhibition and facilitates the preferential translation of ISR-specific mRNAs.

Therapeutic significance:

The protein's involvement in Wolcott-Rallison syndrome, a rare autosomal recessive disorder characterized by insulin-dependent diabetes and multisystem manifestations, highlights its therapeutic significance. Understanding the role of Eukaryotic translation initiation factor 2-alpha kinase 3 could open doors to potential therapeutic strategies for managing this syndrome and related metabolic and stress response disorders.