AP14145 hydrochloride is a potent K Ca 2 (SK) channel negative allosteric modulator with an IC 50 of 1.1 μM for K Ca 2.2 (SK2) and K Ca 2.3 (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).

AP14145 (10 nM-30 μM) inhibits both hK Ca 2.2 and hK Ca 2.3 channel currents in a concentration‐dependent fashion. AP14145 (10 μM) inhibits 50% of the hK Ca 1.1 current, 90% of the hK Ca 2.1 current and has no effect on hK Ca 3.1 channel. AP14145 (10 μM) increases the EC 50 of Ca 2+ on K Ca 2.3 channels from 0.36 to 1.2 μM[1]. AP14145 hydrochloride demonstrates an IC 50 in whole-cell patch clamp on the human SK3 channel of 1.3 μM. AP14145 inhibits hERG (K V 11.1) with an IC 50 of 71.8 μM and K ir 3.1/K ir 3.4 (I KACh ) with an IC 50 of 9.3 μM and does not produce any significant effects on K V 1.5 (I Kur ), K V 7.1/KCNE1 (I Ks ), K V 4.3/KChiP2 (I to ), and K ir 2.1 (I K1 ) in 30 μM or on Na V 1.5 (15 μM; I Na ) on a panel of cardiac ion channels. AP14145 (1-10 μM) produces no significant block of Ca V 1.2[2].

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 ? of 24.3 minutes in landrace pigs (12-13 weeks old, 30-35 kg gilts)[2].

2387505-59-9

C18H18ClF3N4O

398.81

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years