kv7.2

Kv7.2 Kv7.3 agonist 1 (Compound 16) is an orally effective agonist for the KV7.2 7.3 channels (KV7.2 7.3 channel KCNQ2 3) with an EC50 of 1.03 μM. This compound demonstrates analgesic effects in mouse models of chronic constriction injury (CCI) and Streptozotocin-induced diabetic peripheral neuropathy (DPNP), with ED50 values of 12.02 mg kg and 9.63 mg kg, respectively.

Kv7.2 Kv7.3 Activator-1 (compound 517) serves as a powerful activator of the Kv7.2 Kv7.3 channels, exhibiting an EC50 value of less than 1 µM. It holds potential for use in neurological disease research.

Kv7.2 Modulator 1 (compound 10), a modulator of the Kv7.2 channel, is utilized in epilepsy research.

ZTZ240 is a KCNQ2 channel activator used in the study of epilepsy.

XE991 is a novel and selective Kv7 (KCNQ) channel blocker.XE 991 dihydrochloride inhibits Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), Kv7.2 + Kv7.3 (KCNQ3) channels, and M-current, and can be used for the study of neurological diseases.

ICA-105665 (PF-04895162) is a potent and orally active opener of neuronal Kv7.2 7.3 and Kv7.3 7.5 potassium channels. ICA-105665 had low cytotoxic potential in human hepatocytes but inhibited liver mitochondrial function and bile salt export protein (BSEP) transport (IC50 of 311 μM). ICA-105665 can penetrate the central nervous system (CNS) and has antiseizure effects [1][2][3][4].

XE 991 dihydrochloride is a Kv7 (KCNQ) channel blocker. XE 991 dihydrochloride potently inhibits Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), Kv7.2 + Kv7.3 (KCNQ3) channel, and M-current (IC50s: 0.75 μM, 0.71 μM, 0.6 μM, and 0.98 μM, respectively).

QO-58 is a Kv7 channel opener with EC50 values of 7.0, 1.0, 5.2, 0.6 μM for Kv7.1, Kv7.2, Kv7.3/7.5, Kv7.4 respectively. QO-58 increases the pain threshold of neuropathic pain in a sciatic nerve CCI in vivo.

ML213 (CID-3111211) is a selective activator of Kv7.2 (KCNQ2) and Kv7.4 (KCNQ4) channels, enhances Kv7.2 and Kv7.4 channels with EC50s of 230 and 510 nM, respectively.

ML252 is a selective potassium channel inhibitor, specifically targeting the KCNQ2 channel (Kv7.2) with an IC50 value of 69 nM. Additionally, ML252 demonstrates inhibitory activity against Cytochrome P450 isoforms, including IC50 values of 6.1 nM (CYP1A2), 18.9 nM (CYP2C9), 3.9 nM (CYP3A4), and 19.9 nM (CYP2D6).

PF05020182 is novel potent and selective Kv7.2 4 potassium channel opener. PF-05020182 (2) significantly inhibits convulsions in the MES assay at doses tested, consistent with in vitro activity measure. The physiochemical properties, in vitro and in vivo activities of PF-05020182 support further development as an adjunctive treatment of refractory epilepsy. Facilitating activation, or delaying inactivation, of the native Kv7 channel reduces neuronal excitability, which may be beneficial in controlling spontaneous electrical activity during epileptic seizures.

ML-252 is a potent, selective inhibitor of the Kv7.2 voltage-gated potassium channel, demonstrating an IC50 value of 69 nM in patch clamp assays. It exists as the (S)-enantiomer, which is significantly more effective than both its (R)-enantiomer counterpart and the racemic mixture, with respective IC50 values of 944 nM and 160 nM. ML-252 exhibits high selectivity for Kv7.2 over other potassium channel subtypes and shows minimal activity against more than 68 G protein-coupled receptors, various transporters, L- and N-type calcium channels, K_ATP, and hERG potassium channels. However, it does inhibit the melatonin MT1 receptor by 61% at a 10 µM concentration.

KCNQ2 3 activator-1 is a Kv7.2 Kv7.3 (KCNQ2 3) potassium channel activator, details of which are from Compound A of Patent WO2021113757A1.