Focused On-demand Library for NPC intracellular cholesterol transporter 1

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The focused library is created on demand with the latest virtual screening and parameter assessment technology, supported by the Receptor.AI drug discovery platform. This method is more effective than traditional methods and results in higher-quality compounds with better activity, selectivity, and safety.

We carefully select specific compounds from a vast collection of over 60 billion molecules in virtual chemical space. Our partner Reaxense helps in synthesizing and delivering these compounds.

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

It includes in-depth molecular simulations of both the catalytic and allosteric binding pockets, with ensemble virtual screening focusing on their conformational flexibility. For modulators, the process includes considering the structural shifts due to reaction intermediates to boost 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

O15118

UPID:

NPC1_HUMAN

Alternative names:

Niemann-Pick C1 protein

Alternative UPACC:

O15118; B4DET3; Q9P130

Background:

NPC intracellular cholesterol transporter 1, also known as Niemann-Pick C1 protein, plays a pivotal role in cholesterol homeostasis. It facilitates the egress of cholesterol from the endosomal/lysosomal compartment, crucial for cellular lipid balance. The protein interacts with NPC2 for cholesterol transfer and binds oxysterol with higher affinity, indicating a nuanced role in lipid signaling and metabolism.

Therapeutic significance:

Niemann-Pick disease C1, a lysosomal storage disorder, is directly linked to mutations in the gene encoding this protein. Understanding its function and the molecular mechanisms underlying its interaction with cholesterol and other molecules could pave the way for targeted therapies, potentially alleviating the severe neurological and visceral symptoms associated with this condition.