Focused On-demand Library for Serine/threonine-protein kinase VRK1

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.

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 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 comprehensive molecular simulations of the catalytic and allosteric binding pockets and the ensemble virtual screening accounting for their conformational mobility. In the case of designing modulators, the structural changes induced by reaction intermediates are taken into account to leverage 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

Q99986

UPID:

VRK1_HUMAN

Alternative names:

Vaccinia-related kinase 1

Alternative UPACC:

Q99986; Q3SYL2

Background:

Serine/threonine-protein kinase VRK1, also known as Vaccinia-related kinase 1, plays a pivotal role in cell cycle regulation, nuclear condensation, and transcription regulation. It is instrumental in Golgi disassembly during mitosis, phosphorylates p53/TP53 to potentially regulate its interaction with MDM2, and activates ATF2's transcriptional activity through phosphorylation. VRK1's involvement in DNA damage response is highlighted by its phosphorylation of KAT5, enhancing chromatin association and histone acetyltransferase activity.

Therapeutic significance:

VRK1's mutation is linked to Pontocerebellar hypoplasia 1A, a severe neurological disorder characterized by motor dysfunction, muscle hypotonia, and respiratory insufficiency. Understanding the role of Serine/threonine-protein kinase VRK1 could open doors to potential therapeutic strategies for this debilitating condition.