Focused On-demand Library for Voltage-dependent L-type calcium channel subunit alpha-1S

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.

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.

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

Fig. 1. The sreening workflow of Receptor.AI

It includes extensive molecular simulations of the channel in its native membrane environment in open, closed and inactivated forms and the ensemble virtual screening accounting for conformational mobility in each of these states. Tentative binding pockets are considered inside the pore, in the gating region and in the allosteric locations to cover the whole spectrum of possible mechanisms of action.

Our library distinguishes itself through several key aspects:

The Receptor.AI platform integrates all available data about the target protein, including past experiments, literature data, known ligands, structural information and more. This consolidated approach maximises the probability of prioritising highly relevant compounds.
The platform uses sophisticated molecular simulations to identify possible binding sites so that the compounds in the focused library are suitable for discovering allosteric inhibitors and the binders for cryptic pockets.
The platform integrates over 50 highly customisable AI models, which are thoroughly tested and validated on a multitude of commercial drug discovery programs and research projects. It is designed to be efficient, reliable and accurate. All this power is utilised when producing the focused libraries.
In addition to producing the focused libraries, Receptor.AI provides services and end-to-end solutions at every stage of preclinical drug discovery. The pricing model is success-based, which reduces your risks and leverages the mutual benefits of the project's success.

partner

Reaxense

upacc

Q13698

UPID:

CAC1S_HUMAN

Alternative names:

Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle; Voltage-gated calcium channel subunit alpha Cav1.1

Alternative UPACC:

Q13698; A4IF51; B1ALM2; Q12896; Q13934

Background:

The Voltage-dependent L-type calcium channel subunit alpha-1S, also known as Cav1.1, is a pivotal pore-forming component of the L-type calcium channel in skeletal muscle. It plays a crucial role in excitation-contraction coupling, a process essential for muscle contraction, by facilitating the influx of calcium ions upon membrane depolarization. This interaction with the ryanodine receptor (RYR1) triggers calcium release from the sarcoplasmic reticulum.

Therapeutic significance:

Given its central role in skeletal muscle function, mutations in the Cav1.1 gene are linked to several neuromuscular disorders, including Hypokalemic Periodic Paralysis, Malignant Hyperthermia, Thyrotoxic Periodic Paralysis, and Congenital Myopathy. Understanding the molecular mechanisms of Cav1.1 could lead to targeted therapies for these conditions, highlighting the protein's therapeutic significance.