Focused On-demand Library for Voltage-dependent R-type calcium channel subunit alpha-1E

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.

Contained in the library are leading modulators, each labelled with 38 ADME-Tox and 32 physicochemical and drug-likeness qualities. In addition, each compound is illustrated with its optimal docking poses, affinity scores, and activity scores, giving a complete picture.

We utilise our cutting-edge, exclusive workflow to develop focused libraries for ion channels.

Fig. 1. The sreening workflow of Receptor.AI

The method involves in-depth molecular simulations of the ion channel in its native membrane environment, including its open, closed, and inactivated states, along with ensemble virtual screening that focuses on conformational mobility for each state. Tentative binding pockets are identified inside the pore, in the gating area, and at allosteric sites to address every conceivable mechanism of action.

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

Q15878

UPID:

CAC1E_HUMAN

Alternative names:

Brain calcium channel II; Calcium channel, L type, alpha-1 polypeptide, isoform 6; Voltage-gated calcium channel subunit alpha Cav2.3

Alternative UPACC:

Q15878; B1AM12; B1AM13; B1AM14; Q14580; Q14581

Background:

The Voltage-dependent R-type calcium channel subunit alpha-1E, known alternatively as Brain calcium channel II, plays a pivotal role in mediating calcium ion entry into neurons. This process is crucial for a myriad of cellular functions including muscle contraction, neurotransmitter release, and cell division. The alpha-1E subunit is distinctive for generating R-type calcium currents, part of the high-voltage activated group, and shows insensitivity to dihydropyridines.

Therapeutic significance:

Linked to Developmental and epileptic encephalopathy 69 (DEE69), a severe neurological disorder characterized by refractory seizures and neurodevelopmental impairment, the alpha-1E subunit's modulation of neuronal firing patterns presents a potential target for therapeutic intervention. Understanding its role could lead to novel treatments for DEE69, especially considering some patients' favorable response to topiramate.