Focused On-demand Library for Vitamin K-dependent gamma-carboxylase

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.

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.

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.

We utilise our cutting-edge, exclusive workflow to develop focused 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

P38435

UPID:

VKGC_HUMAN

Alternative names:

Gamma-glutamyl carboxylase; Peptidyl-glutamate 4-carboxylase; Vitamin K gamma glutamyl carboxylase

Alternative UPACC:

P38435; B4DMC5; E9PEE1; Q14415; Q6GU45

Background:

Vitamin K-dependent gamma-carboxylase plays a pivotal role in the post-translational modification of proteins involved in blood coagulation, bone metabolism, and cardiovascular health. It catalyzes the vitamin K-dependent carboxylation of glutamate residues, a critical process for the activation of several coagulation factors and other proteins such as osteocalcin and matrix Gla protein.

Therapeutic significance:

The protein's malfunction is linked to Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD) and Pseudoxanthoma elasticum-like disorder, both characterized by coagulation impairments and, in the latter, severe skin laxity. Understanding the role of Vitamin K-dependent gamma-carboxylase could open doors to potential therapeutic strategies for these conditions.