KB-130015

KB-130015 is an antiarrhythmic agent and a derivative of amiodarone .¹ It inhibits potassium currents induced by acetylcholine or adenosine in isolated guinea pig atrial myocytes (IC₅₀s = 0.82 and 0.57 µM, respectively).² KB-130015 activates or inhibits the voltage-gated potassium channel human-ether-a-go-go (hERG), also known as K_v11.1, in HEK293 cells in a voltage-dependent manner.³ It activates large-conductance calcium-activated potassium (BK_Ca) channels in HEK293 cells expressing the BK_Ca subunit Slo1 (EC₅₀ = 20.2 μM).⁴ KB-130015 (40 mg/kg) prolongs the duration of electrically stimulated action potentials in guinea pig papillary muscle ex vivo.¹ It is also an antagonist of human thyroid hormone receptor α (TRα) and TRβ (IC₅₀s = 2.2 and 4.1 µM, respectively, in reporter assays).

1.Carlsson, B., Singh, B.N., Temciuc, M., et al.Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodaroneJ. Med. Chem.45(3)623-630(2002) 2.Brandts, B., Borchard, R., Macianskiene, R., et al.Inhibition of G protein-coupled and ATP-sensitive potassium currents by 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015), an amiodarone derivativeJ. Pharmacol. Exp. Ther.308(1)134-142(2004) 3.Gessner, G., Macianskiene, R., Starkus, J.G., et al.The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanismEur. J. Pharmacol.632(1-3)52-59(2010) 4.Gessner, G., Heller, R., Hoshi, T., et al.The amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) opens large-conductance Ca2+-activated K+ channels and relaxes vascular smooth muscleEur. J. Pharmacol.555(2-3)185-193(2007)