Focused On-demand Library for Lys-63-specific deubiquitinase BRCC36

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.

We carefully select specific compounds from a vast collection of over 60 billion molecules in virtual chemical space. Our partner Reaxense helps in synthesizing and delivering these compounds.

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

The procedure entails thorough molecular simulations of the catalytic and allosteric binding pockets, accompanied by ensemble virtual screening that factors in their conformational flexibility. When developing modulators, the structural modifications brought about by reaction intermediates are factored in to optimize 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

P46736

UPID:

BRCC3_HUMAN

Alternative names:

BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 3; BRCA1/BRCA2-containing complex subunit 36; BRISC complex subunit BRCC36

Alternative UPACC:

P46736; A6QRF8; A6QRF9; A8MUX5; A8MWH0; A9Z1Y0; A9Z1Y5; B1B062; B4DQN7; Q16107; Q53YX5; Q9BTZ6

Background:

Lys-63-specific deubiquitinase BRCC36, a pivotal component of the BRCA1-A complex, plays a crucial role in DNA damage response by specifically cleaving 'Lys-63'-linked polyubiquitin chains. Unlike its inactivity towards 'Lys-48'-linked chains, BRCC36's unique specificity aids in the recognition and repair of DNA lesions by removing ubiquitin from histones H2A and H2AX, facilitating the recruitment of repair complexes to double-strand breaks. Additionally, as part of the BRISC complex, it contributes to various cellular processes, including mitotic spindle assembly and interferon signaling, by deubiquitinating key substrates.

Therapeutic significance:

Understanding the role of Lys-63-specific deubiquitinase BRCC36 could open doors to potential therapeutic strategies, especially in enhancing DNA repair mechanisms and modulating immune responses, which are critical in cancer and inflammatory diseases.