Focused On-demand Library for Proprotein convertase subtilisin/kexin type 9

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The specialised, focused library is developed on demand with the most recent virtual screening and parameter assessment technology, guided by the Receptor.AI drug discovery platform. This approach exceeds the capabilities of traditional methods and offers compounds with higher 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.

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

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.

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

Q8NBP7

UPID:

PCSK9_HUMAN

Alternative names:

Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9

Alternative UPACC:

Q8NBP7; A8T640; C0JYY9; Q5PSM5; Q5SZQ2

Background:

Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as Neural apoptosis-regulated convertase 1, plays a pivotal role in cholesterol homeostasis. It binds to and promotes the degradation of receptors crucial for low-density lipoprotein (LDL) clearance, such as LDLR and VLDLR. PCSK9's influence extends to modulating epithelial sodium channels, impacting sodium absorption.

Therapeutic significance:

Given its central role in regulating LDL cholesterol levels, PCSK9 is directly implicated in familial hypercholesterolemia, a condition leading to premature coronary heart disease. Targeting PCSK9 offers a promising avenue for therapeutic intervention in managing elevated cholesterol levels and associated cardiovascular risks.