Focused On-demand Library for Pyruvate kinase PKM

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The specialised, focused library is developed on demand with the most recent virtual screening and parameter assessment technology, guided by the Receptor.AI drug discovery platform. This approach exceeds the capabilities of traditional methods and offers compounds with higher 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 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.

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

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

P14618

UPID:

KPYM_HUMAN

Alternative names:

Cytosolic thyroid hormone-binding protein; Opa-interacting protein 3; Pyruvate kinase 2/3; Pyruvate kinase muscle isozyme; Threonine-protein kinase PKM2; Thyroid hormone-binding protein 1; Tumor M2-PK; Tyrosine-protein kinase PKM2; p58

Alternative UPACC:

P14618; A6NFK3; B2R5N8; B3KRY0; B4DFX8; B4DUU6; P14786; Q53GK4; Q96E76; Q9BWB5; Q9UCV6; Q9UPF2

Background:

Pyruvate kinase PKM, with alternative names such as Pyruvate kinase muscle isozyme and Tyrosine-protein kinase PKM2, plays a pivotal role in glycolysis. It catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. This enzyme exists in a dynamic equilibrium between a highly active tetrameric form and a nearly inactive dimeric form, crucial for metabolic flux regulation. Additionally, PKM2 isoforms exhibit diverse functionalities, including acting as a protein kinase in the nucleus, influencing transcription and promoting cell proliferation in cancer cells.

Therapeutic significance:

Understanding the role of Pyruvate kinase PKM could open doors to potential therapeutic strategies.