Focused On-demand Library for General transcription and DNA repair factor IIH helicase subunit XPD

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The focused library is created on demand with the latest virtual screening and parameter assessment technology, supported by the Receptor.AI drug discovery platform. This method is more effective than traditional methods and results in higher-quality compounds with better 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 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.

Our library stands out due to several important features:

The Receptor.AI platform compiles comprehensive data on the target protein, encompassing previous experiments, literature, known ligands, structural details, and more, leading to a higher chance of selecting the most relevant compounds.
Advanced molecular simulations on the platform help pinpoint potential binding sites, making the compounds in our focused library ideal for finding allosteric inhibitors and targeting cryptic pockets.
Receptor.AI boasts over 50 tailor-made AI models, rigorously tested and proven in various drug discovery projects and research initiatives. They are crafted for efficacy, dependability, and precision, all of which are key in creating our focused libraries.
Beyond creating focused libraries, Receptor.AI offers comprehensive services and complete solutions throughout the preclinical drug discovery phase. Our success-based pricing model minimises risk and maximises the mutual benefits of the project's success.

partner

Reaxense

upacc

P18074

UPID:

ERCC2_HUMAN

Alternative names:

Basic transcription factor 2 80 kDa subunit; CXPD; DNA excision repair protein ERCC-2; DNA repair protein complementing XP-D cells; TFIIH basal transcription factor complex 80 kDa subunit; Xeroderma pigmentosum group D-complementing protein

Alternative UPACC:

P18074; Q2TB78; Q2YDY2; Q7KZU6; Q8N721

Background:

The General transcription and DNA repair factor IIH helicase subunit XPD, known by alternative names such as DNA repair protein complementing XP-D cells and Xeroderma pigmentosum group D-complementing protein, plays a pivotal role in DNA repair and transcription. It is a key component of the TFIIH core complex, essential for nucleotide excision repair (NER) and transcription initiation by RNA polymerase II. Its ATP-dependent helicase activity is crucial for DNA opening during NER and transcription initiation, highlighting its multifaceted role in cellular DNA integrity and gene expression.

Therapeutic significance:

Given its critical functions in DNA repair and transcription, XPD is directly implicated in diseases such as Xeroderma pigmentosum complementation group D, Trichothiodystrophy 1, photosensitive, and Cerebro-oculo-facio-skeletal syndrome 2. These conditions underscore the protein's therapeutic significance, as understanding and targeting XPD's mechanisms could lead to innovative treatments for these genetic disorders, emphasizing the importance of research in this area.