Focused On-demand Library for Calcium-activated potassium channel subunit alpha-1

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.

Our selection of compounds is from a large virtual library of over 60 billion molecules. The production and distribution of these compounds are managed by our partner Reaxense.

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

Q12791

UPID:

KCMA1_HUMAN

Alternative names:

BK channel; BKCA alpha; Calcium-activated potassium channel, subfamily M subunit alpha-1; K(VCA)alpha; KCa1.1; Maxi K channel; Slo-alpha; Slo1; Slowpoke homolog

Alternative UPACC:

Q12791; F8WA96; Q12886; Q12917; Q12921; Q12960; Q13150; Q5JQ23; Q5SQR9; Q96LG8; Q9UBB0; Q9UCX0; Q9UQK6

Background:

The Calcium-activated potassium channel subunit alpha-1, known as KCa1.1 or BK channel, plays a pivotal role in cellular excitability. By mediating K+ export in response to membrane depolarization and cytosolic Ca2+ increase, it contributes to the repolarization of the membrane potential. Its activity is crucial in various systems, including smooth muscle contraction, cochlear hair cell tuning, neurotransmitter release, and innate immunity.

Therapeutic significance:

KCa1.1 is implicated in several neurological disorders, including Paroxysmal nonkinesigenic dyskinesia, Epilepsy, idiopathic generalized 16, and Liang-Wang syndrome. Understanding the role of KCa1.1 could open doors to potential therapeutic strategies for these conditions.