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

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.

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.

The library includes a list of the most promising modulators annotated with 38 ADME-Tox and 32 physicochemical and drug-likeness parameters. Also, each compound is presented with its optimal docking poses, affinity scores, and activity scores, providing a comprehensive overview.

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 stands out due to several important features:

The Receptor.AI platform compiles comprehensive data on the target protein, encompassing previous experiments, literature, known ligands, structural details, and more, leading to a higher chance of selecting the most relevant compounds.
Advanced molecular simulations on the platform help pinpoint potential binding sites, making the compounds in our focused library ideal for finding allosteric inhibitors and targeting cryptic pockets.
Receptor.AI boasts over 50 tailor-made AI models, rigorously tested and proven in various drug discovery projects and research initiatives. They are crafted for efficacy, dependability, and precision, all of which are key in creating our focused libraries.
Beyond creating focused libraries, Receptor.AI offers comprehensive services and complete solutions throughout the preclinical drug discovery phase. Our success-based pricing model minimises risk and maximises the mutual benefits of the project's 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.