Focused On-demand Library for Phosphate-regulating neutral endopeptidase PHEX

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

This comprehensive focused library is produced on demand with state-of-the-art virtual screening and parameter assessment technology driven by Receptor.AI drug discovery platform. This approach outperforms traditional methods and provides higher-quality compounds with superior 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.

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.

Our top-notch dedicated system is used to design specialised libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

The procedure entails thorough molecular simulations of the catalytic and allosteric binding pockets, accompanied by ensemble virtual screening that factors in their conformational flexibility. When developing modulators, the structural modifications brought about by reaction intermediates are factored in to optimize 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

P78562

UPID:

PHEX_HUMAN

Alternative names:

Metalloendopeptidase homolog PEX; Vitamin D-resistant hypophosphatemic rickets protein; X-linked hypophosphatemia protein

Alternative UPACC:

P78562; O00678; Q13646; Q2M325; Q93032; Q99827

Background:

Phosphate-regulating neutral endopeptidase PHEX, also known as Metalloendopeptidase homolog PEX, plays a pivotal role in bone mineralization and renal phosphate reabsorption. It functions by cleaving SIBLING-derived ASARM peptides, which are crucial for regulating osteogenic cell differentiation and promoting dentin mineralization. The protein's activity is essential for the proper biological functioning of these peptides, influencing skeletal development and phosphate metabolism.

Therapeutic significance:

PHEX's malfunction is directly linked to Hypophosphatemic rickets, X-linked dominant, a disorder impairing phosphate uptake due to abnormal sodium phosphate cotransport regulation. This condition manifests in skeletal deformities and growth failure, highlighting the protein's critical role in bone health. Understanding the role of Phosphate-regulating neutral endopeptidase PHEX could open doors to potential therapeutic strategies for treating bone mineralization disorders and improving phosphate metabolism.