Focused On-demand Library for Hydroxymethylglutaryl-CoA lyase, mitochondrial

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.

The compounds are cherry-picked from the vast virtual chemical space of over 60B molecules. The synthesis and delivery of compounds is facilitated by our partner Reaxense.

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.

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 is unique due to several crucial aspects:

Receptor.AI compiles all relevant data on the target protein, such as past experimental results, literature findings, known ligands, and structural data, thereby enhancing the likelihood of focusing on the most significant compounds.
By utilizing advanced molecular simulations, the platform is adept at locating potential binding sites, rendering the compounds in the focused library well-suited for unearthing allosteric inhibitors and binders for hidden pockets.
The platform is supported by more than 50 highly specialized AI models, all of which have been rigorously tested and validated in diverse drug discovery and research programs. Its design emphasizes efficiency, reliability, and accuracy, crucial for producing focused libraries.
Receptor.AI extends beyond just creating focused libraries; it offers a complete spectrum of services and solutions during the preclinical drug discovery phase, with a success-dependent pricing strategy that reduces risk and fosters shared success in the project.

partner

Reaxense

upacc

P35914

UPID:

HMGCL_HUMAN

Alternative names:

3-hydroxy-3-methylglutarate-CoA lyase

Alternative UPACC:

P35914; B4DUP4; B7UCC6; D3Y5K7; Q6IBC0; Q96FP8

Background:

Hydroxymethylglutaryl-CoA lyase, mitochondrial, also known as 3-hydroxy-3-methylglutarate-CoA lyase, plays a pivotal role in ketogenesis and leucine catabolism. This enzyme catalyzes the cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, essential for energy production and lipid synthesis.

Therapeutic significance:

The deficiency of Hydroxymethylglutaryl-CoA lyase, mitochondrial, leads to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. This autosomal recessive disease manifests in acute symptoms like vomiting, seizures, and metabolic acidosis, potentially progressing to coma or fatal outcomes. Understanding its role could pave the way for innovative treatments.