Focused On-demand Library for Prolyl 3-hydroxylase 1

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 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 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.

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.

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

Q32P28

UPID:

P3H1_HUMAN

Alternative names:

Growth suppressor 1; Leucine- and proline-enriched proteoglycan 1

Alternative UPACC:

Q32P28; Q7KZR4; Q96BR8; Q96SK8; Q96SL5; Q96SN3; Q9H6K3; Q9HC86; Q9HC87

Background:

Prolyl 3-hydroxylase 1, also known as Growth suppressor 1 and Leucine- and proline-enriched proteoglycan 1, plays a pivotal role in collagen biosynthesis. It catalyzes the post-translational formation of 3-hydroxyproline in collagens, particularly types IV and V, which are essential for the structural integrity and function of connective tissues. This enzyme is also associated with the basement membrane and may influence cell secretory pathways and fibroblast growth suppression.

Therapeutic significance:

Prolyl 3-hydroxylase 1 is directly implicated in Osteogenesis imperfecta 8, a disorder characterized by bone fragility and susceptibility to fractures. The disease is linked to mutations affecting this enzyme, leading to severe collagen hydroxylation defects. Understanding the role of Prolyl 3-hydroxylase 1 in collagen biosynthesis and its mutations could pave the way for novel therapeutic strategies targeting bone disorders and improving patient outcomes.