Focused On-demand Library for E3 ubiquitin-protein ligase MARCHF6

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.

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.

Our high-tech, dedicated method is applied to construct targeted 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

O60337

UPID:

MARH6_HUMAN

Alternative names:

Doa10 homolog; Membrane-associated RING finger protein 6; Membrane-associated RING-CH protein VI; Protein TEB-4; RING finger protein 176; RING-type E3 ubiquitin transferase MARCHF6

Alternative UPACC:

O60337; A5PKZ4; B4DKJ2; B4DT33; D3DTC8; O14670; Q86X77

Background:

E3 ubiquitin-protein ligase MARCHF6, also known as Membrane-associated RING-CH protein VI, plays a pivotal role in protein homeostasis by promoting 'Lys-48'-linked ubiquitination. This process targets proteins such as DIO2 and SQLE for proteasomal degradation, crucial for cellular function and health.

Therapeutic significance:

Linked to Epilepsy, familial adult myoclonic, 3 (FAME3), MARCHF6's involvement in neurological disorders highlights its potential as a therapeutic target. Understanding MARCHF6's role could pave the way for innovative treatments for epilepsy and related conditions.