Focused On-demand Library for Lysosomal cobalamin transporter ABCD4

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

This extensive focused library is tailor-made using the latest virtual screening and parameter assessment technology, operated by the Receptor.AI drug discovery platform. This technique is more effective than traditional methods, offering compounds with improved activity, selectivity, and safety.

From a virtual chemical space containing more than 60 billion molecules, we precisely choose certain compounds. Our collaborator, Reaxense, aids in their synthesis and provision.

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 employ our advanced, specialised process to create targeted libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

This approach involves comprehensive molecular simulations of the catalytic and allosteric binding pockets and ensemble virtual screening that accounts for their conformational flexibility. In the case of designing modulators, the structural adjustments caused by reaction intermediates are considered to improve activity and selectivity.

Key features that set our library apart include:

The Receptor.AI platform integrates extensive information about the target protein, such as historical experiments, academic research, known ligands, and structural insights, thereby increasing the likelihood of identifying highly relevant compounds.
The platform’s sophisticated molecular simulations are designed to discover potential binding sites, ensuring that our focused library is optimal for the discovery of allosteric inhibitors and binders for cryptic pockets.
With over 50 customisable AI models, verified through extensive testing in commercial drug discovery and research, Receptor.AI is efficient, reliable, and precise. These models are essential in the production of our focused libraries.
Receptor.AI not only produces focused libraries but also provides full services and solutions at every stage of preclinical drug discovery, with a success-based pricing structure that aligns our interests with the success of your project.

partner

Reaxense

upacc

O14678

UPID:

ABCD4_HUMAN

Alternative names:

ATP-binding cassette sub-family D member 4; PMP70-related protein; Peroxisomal membrane protein 1-like; Peroxisomal membrane protein 69

Alternative UPACC:

O14678; A8K5L7; Q6IAQ0; Q96E75

Background:

The Lysosomal cobalamin transporter ABCD4, also known as ATP-binding cassette sub-family D member 4, plays a crucial role in the transport of cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol. This process is vital for maintaining proper cellular function and is facilitated by an ATP-dependent mechanism. ABCD4's interaction with the lysosomal chaperone LMBRD1 and cytosolic MMACHC is essential for the efficient transport of cobalamin across the lysosomal membrane.

Therapeutic significance:

ABCD4's dysfunction is linked to Methylmalonic aciduria and homocystinuria type cblJ, a metabolic disorder characterized by decreased levels of adenosylcobalamin and methylcobalamin, leading to severe clinical features such as anemia and developmental delay. Understanding the role of ABCD4 could open doors to potential therapeutic strategies for treating this disorder.