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 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.

We pick out particular compounds from an extensive virtual database of more than 60 billion molecules. The preparation and shipment of these compounds are facilitated by our associate 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.

Our high-tech, dedicated method is applied to construct targeted libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

The method includes detailed molecular simulations of the catalytic and allosteric binding pockets, along with ensemble virtual screening that considers their conformational flexibility. In the design of modulators, structural changes induced by reaction intermediates are taken into account to enhance activity and selectivity.

Our library distinguishes itself through several key aspects:

The Receptor.AI platform integrates all available data about the target protein, including past experiments, literature data, known ligands, structural information and more. This consolidated approach maximises the probability of prioritising highly relevant compounds.
The platform uses sophisticated molecular simulations to identify possible binding sites so that the compounds in the focused library are suitable for discovering allosteric inhibitors and the binders for cryptic pockets.
The platform integrates over 50 highly customisable AI models, which are thoroughly tested and validated on a multitude of commercial drug discovery programs and research projects. It is designed to be efficient, reliable and accurate. All this power is utilised when producing the focused libraries.
In addition to producing the focused libraries, Receptor.AI provides services and end-to-end solutions at every stage of preclinical drug discovery. The pricing model is success-based, which reduces your risks and leverages the mutual benefits of the project's success.

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.