KB130015

KB130015 (KB015) is an orally active and potent ThRα and ThRβ (thyroid hormone receptor) inhibitor, with IC₅₀ values of 4.5 and 5.1 μM, respectively. KB130015 markedly slows the kinetics of inactivation of Na⁺ channels. KB130015 activates hERG1 channels (EC₅₀ = 12.2 μM) and large-conductance Ca²⁺-activated K⁺ (BKCa) channels formed by hSlo1 (α) subunits in HEK 293 cells. KB130015 has antiarrhythmic properties. KB130015 can be used for the study of cardiovascular disease^[1][2][3][4]. IC50 & Target:IC₅₀: 4.5 μM (ThRα), 5.1 μM (ThRβ)^[1] In Vitro:KB130015 (1-10 μM) slows the inactivation kinetics of cardiac Na⁺ channels by enhancing a slow-inactivating I_Na component at the expense of the fast-inactivating component in guinea pig, rabbit, and pig ventricular myocytes^[2].
KB130015 shifts the steady-state voltage-dependent inactivation of Na⁺ channels to more negative potentials and slows the recovery from inactivation in cardiac myocytes^[2].
KB130015 (10 μM) decreases the amplitude of L-type Ca²⁺current (Ica-L) by about 30% without changing its inactivation time course in pig ventricular myocytes^[2].
KB130015 (50 μM) exerts a positive inotropic action by increasing cell shortening amplitude in pig ventricular myocytes without altering the time course^[2].
KB130015 (100 μM) shortens the action potential duration (APD) in pig ventricular trabeculum but prolongs short APDs and induces early afterdepolarizations (EADs) in mouse left ventricular papillary muscle^[2].
KB130015 (100 μM) activates large-conductance Ca²⁺-activated K⁺ (BKCa) channels formed by hSlo1 (α) subunits in HEK 293 cells and the BKCa channels from insects (Drosophila melanogaster dSlo and Periplaneta americana pSlo) expressed in HEK 293 cells^[3].
In Vivo:KB130015 (40 mg/kg, i.p., daily, 20 days) significantly prolongs APD50, APD90 and ERP, decreases V_max without changing APA and RP in guinea pig ventricular papillary muscle^[1].
KB130015 (30-300 mg/kg, p.o., daily, 2 weeks) alters thyroid hormone levels (reduces T3, increases T4 and TSH) in Sprague-Dawley rats^[1].
KB130015 (20 mg/kg, i.p., daily, 20 days) suppresses ventricular premature beats, ventricular tachycardia and fibrillation during ischemia and reperfusion in rabbits with left anterior descending artery occlusion^[2].