Focused On-demand Library for DNA mismatch repair protein Mlh1

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.

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

Fig. 1. The sreening workflow of Receptor.AI

Our methodology employs molecular simulations to explore a wide array of proteins, capturing their dynamic states both individually and within complexes. Through ensemble virtual screening, we address conformational mobility, uncovering binding sites within functional regions and remote allosteric locations. This thorough exploration ensures no potential mechanism of action is overlooked, aiming to discover novel therapeutic targets and lead compounds across an extensive spectrum of biological functions.

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

P40692

UPID:

MLH1_HUMAN

Alternative names:

MutL protein homolog 1

Alternative UPACC:

P40692; B4DI13; B4DQ11; E9PCU2

Background:

DNA mismatch repair protein Mlh1, also known as MutL protein homolog 1, plays a pivotal role in the post-replicative DNA mismatch repair system (MMR). It forms a heterodimer with PMS2 to create MutL alpha, essential for correcting DNA mismatches and maintaining genomic stability. This protein is also involved in DNA damage signaling, crucial for cell cycle arrest and apoptosis in response to significant DNA damages.

Therapeutic significance:

Mutations in Mlh1 are linked to several hereditary cancers, including Lynch syndrome, Mismatch repair cancer syndrome, Muir-Torre syndrome, and colorectal and endometrial cancers. Understanding the role of DNA mismatch repair protein Mlh1 could open doors to potential therapeutic strategies, offering hope for targeted treatments in these genetically predisposed conditions.