AP14145 hydrochloride 

AP14145 hydrochloride is a potent K_Ca2 (SK) channel negative allosteric modulator with an IC₅₀ of 1.1 μM for K_Ca2.2 (SK2) and K_Ca2.3 (SK3) channels. AP14145 hydrochloride inhibition strongly depends on two amino acids, S508 and A533 in the channel. AP14145 hydrochloride prolonged atrial effective refractory period (AERP) in rats and demonstrates antiarrhythmic effects in a Vernakalant-resistant porcine model of atrial fibrillation (AF)^[1][2].

IC50: 1.1 μM (K_Ca2.2) and 1.1 μM (K_Ca2.3)^[1]

AP14145 (10 nM-30 μM) inhibits both hK_Ca2.2 and hK_Ca2.3 channel currents in a concentration‐dependent fashion. AP14145 (10 μM) inhibits 50% of the hK_Ca1.1 current, 90% of the hK_Ca2.1 current and has no effect on hK_Ca3.1 channel. AP14145 (10 μM) increases the EC₅₀ of Ca²⁺ on K_Ca2.3 channels from 0.36 to 1.2 μM^[1].
AP14145 hydrochloride demonstrates an IC₅₀ in whole-cell patch clamp on the human SK3 channel of 1.3 µM. AP14145 inhibits hERG (K_V11.1) with an IC₅₀ of 71.8 µM and K_ir3.1/K_ir3.4 (I_KACh) with an IC₅₀ of 9.3 µM and does not produce any significant effects on K_V1.5 (I_Kur), K_V7.1/KCNE1 (I_Ks), K_V4.3/KChiP2 (I_to), and K_ir2.1 (I_K1) in 30 µM or on Na_V1.5 (15 µM; I_Na) on a panel of cardiac ion channels. AP14145 (1-10 µM) produces no significant block of Ca_V1.2^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

AP14145 (10 μM) increases the duration of the atrial effective refractory period (AERP) in isolated perfused rat hearts^[1].
AP14145 (2.5 and 5 mg/kg; bolus injections (iv)) increases the duration of the atrial effective refractory period in male sprague-dawley rats (250-350 g, 1-3 months old)^[1].
AP14145 (5 mg/kg; bolus injections) has a C_max of 8355 nmol/L, a t_½ of 24.3 minutes in landrace pigs (12-13 weeks old, 30-35 kg gilts)^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

398.81

C₁₈H₁₈ClF₃N₄O

2387505-59-9

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Rafel Simó-Vicens, et al. A New Negative Allosteric Modulator, AP14145, for the Study of Small Conductance Calcium-Activated Potassium (K_Ca2) Channels. Br J Pharmacol. 2017 Dec;174(23):4396-4408.  [Content Brief]

  [2]. Jonas Goldin Diness, et al. Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca²⁺-Activated K ⁺ Channels in Pigs. Circ Arrhythm Electrophysiol. 2017 Oct;10(10):e005125.  [Content Brief]