KCNQ2 (Kv7.2) Ion Channel Targeted Library

The KCNQ family of voltage-gated potassium channels (Kv) plays an important role in the maintenance of cellular excitability and ion homeostasis since they can facilitate the flow of potassium ions out of cells during the repolarization phase of the action potential. Therefore, KCNQ can regulate the membrane potential of excitable cells such as neurons and myocardium, and plays a crucial role in the maintenance of normal functions of the nervous system and the heart. KCNQ2 and KCNQ3 can form homo- or heterotetramers and are the main molecular basis for the formation of neuronal M-currents. Mutations in the KCNQ2 gene can lead to the development of epileptic encephalopathy. In addition, neuronal hyperexcitability can result in a variety of diseases such as pain, Parkinson's disease, local ischemia, and schizophrenia. Therefore, KCNQ2 is an important drug target associated with many neurological diseases. In animal models, M-current suppression contributes to the development of osteoarthritic pain and neuropathic pain, while KCNQ2 activation is able to relief neuropathic pain and fibromyalgia.

BOC Sciences has designed a novel KCNQ2 (Kv7.2) ion channel targeted library containing approximately 4,600 small drug-like molecules that are potential KCNQ2 activity modulators.

Figure 1. Kv1.3 channels provide the counterbalancing K þ efflux for Ca 2þ entry into CCR7 À T EM-effector cells. (Pennington, M. 2013)

KCNQ2 (Kv7.2) Ion Channel Targeted Library Design

Our experts select compounds for the library using a docking-based virtual screening method against the BOC Sciences HTS compound collections

1. Firstly, two activators ztz240 and retigabine are used to activate KCNQ2 by different mechanisms
2. Then, the human KCNQ2 structure is determined by cryoelectron microscopy in the apo state for in silico screening
3. Immediately after, two different binding sites from KCNQ2 complexes PDBID:7CR1 and PDBID:7CR2 are probed in a virtual screening, generating the screening set containing potential KCNQ activators that are selected based on the highest scoring drug-like screening compounds and their intermolecular contacts within each binding site
4. Finally, PAINS, molecules with undesirable and toxic moieties have been excluded using BOC Sciences’ internal filters

KCNQ2 (Kv7.2) Ion Channel Targeted Library Characteristics

• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of KCNQ2 (Kv7.2) Ion Channel Targeted Library design at competitive prices for global customers. Personalized and customized services of KCNQ2 (Kv7.2) Ion Channel Targeted Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!