Focused On-demand Library for Interferon-inducible double-stranded RNA-dependent protein kinase activator A

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.

Our selection of compounds is from a large virtual library of over 60 billion molecules. The production and distribution of these compounds are managed 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 use our state-of-the-art dedicated workflow for designing focused 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.

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

O75569

UPID:

PRKRA_HUMAN

Alternative names:

PKR-associated protein X; PKR-associating protein X; Protein activator of the interferon-induced protein kinase; Protein kinase, interferon-inducible double-stranded RNA-dependent activator

Alternative UPACC:

O75569; A8K3I6; Q53G24; Q6X7T5; Q8NDK4

Background:

Interferon-inducible double-stranded RNA-dependent protein kinase activator A, also known as PKR-associated protein X, plays a pivotal role in cellular defense mechanisms. It activates EIF2AK2/PKR in the absence of double-stranded RNA, leading to phosphorylation of EIF2S1/EFI2-alpha, inhibiting translation and inducing apoptosis. This protein is essential for siRNA production by DICER1 and subsequent siRNA-mediated gene silencing, although it is not required for pre-miRNA to miRNA processing by DICER1. It also promotes UBC9-p53/TP53 association, sumoylation, and phosphorylation of p53/TP53, enhancing its activity in a EIF2AK2/PKR-dependent manner.

Therapeutic significance:

The association of Interferon-inducible double-stranded RNA-dependent protein kinase activator A with Dystonia 16, a dystonia-parkinsonism disorder, underscores its therapeutic significance. Understanding the role of this protein could lead to novel therapeutic strategies for managing Dystonia 16, characterized by sustained involuntary muscle contraction and parkinsonian features.