AP14145 hydrochloride is a potent KCa2 (SK) channel negative allosteric modulator with an IC50 of 1.1 μM for KCa2.2 (SK2) and KCa2.3 (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).

Product information

CAS Number: 2387505-59-9

Molecular Weight: 398.81

Formula: C18H18ClF3N4O

Chemical Name: N-(2-{[(1R)-1-[3-(trifluoromethyl)phenyl]ethyl]amino}-1H-1,3-benzodiazol-7-yl)acetamide; chlorohydrogen

Smiles: Cl.CC(=O)NC1=CC=CC2N=C(N[C@H](C)C3C=C(C=CC=3)C(F)(F)F)NC=21

InChiKey: KGIUXIYNTCVBST-HNCPQSOCSA-N

InChi: InChI=1S/C18H17F3N4O.ClH/c1-10(12-5-3-6-13(9-12)18(19,20)21)22-17-24-15-8-4-7-14(16(15)25-17)23-11(2)26;/h3-10H,1-2H3,(H,23,26)(H2,22,24,25);1H/t10-;/m1./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

AP14145 (10 nM-30 μM) inhibits both hKCa2.2 and hKCa2.3 channel currents in a concentration‐dependent fashion. AP14145 (10 μM) inhibits 50% of the hKCa1.1 current, 90% of the hKCa2.1 current and has no effect on hKCa3.1 channel. AP14145 (10 μM) increases the EC50 of Ca2+ on KCa2.3 channels from 0.36 to 1.2 μM. AP14145 hydrochloride demonstrates an IC50 in whole-cell patch clamp on the human SK3 channel of 1.3 µM. AP14145 inhibits hERG (KV11.1) with an IC50 of 71.8 µM and Kir3.1/Kir3.4 (IKACh) with an IC50 of 9.3 µM and does not produce any significant effects on KV1.5 (IKur), KV7.1/KCNE1 (IKs), KV4.3/KChiP2 (Ito), and Kir2.1 (IK1) in 30 µM or on NaV1.5 (15 µM; INa) on a panel of cardiac ion channels. AP14145 (1-10 µM) produces no significant block of CaV1.2.

In Vivo:

AP14145 (10 μM) increases the duration of the atrial effective refractory period (AERP) in isolated perfused rat hearts. 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). AP14145 (5 mg/kg; bolus injections) has a Cmax of 8355 nmol/L, a t½ of 24.3 minutes in landrace pigs (12-13 weeks old, 30-35 kg gilts).

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