| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
IC50: 1.1 μM (KCa2.2) and 1.1 μM (KCa2.3)[1]
KCa2.2 (SK2) and KCa2.3 (SK3) channels (negative allosteric modulator, IC50 = 1.1 microM each). |
|---|---|
| ln Vitro |
The concentration-dependent inhibition of hKCa2.2 and hKCa2.3 channel currents is observed with AP14145 (10 nM-30 μM). 50% of the hKCa1.1 current and 90% of the hKCa2.1 current are inhibited by AP14145 (10 μM), whereas the hKCa3.1 channel is unaffected. On KCa2.3 channels, AP14145 (10 μM) raises the Ca2+ EC50 from 0.36 to 1.2 μM[1]. The hydrochloride AP14145 has an IC50 of 1.3 µM in whole-cell patch clamp on the human SK3 channel. On a panel of cardiac ion channels, AP14145 has no discernible effects on KV1.5 (IKur), KV7.1/KCNE1 (IKs), KV4.3/KChiP2 (Ito), or Kir2.1 (IK1) at 30 µM or on NaV1.5 (15 µM; INa). It suppresses hERG (KV11.1) with an IC50 of 71.8 µM and Kir3.1/Kir3.4 (IKACh) with an IC50 of 9.3 µM. One cannot produce a significant block of CaV1.2 with AP14145 (1–10 µM)[2].
AP14145 (10 microM) inhibits 50% of hKCa1.1 current, 90% of hKCa2.1 current, and has no effect on hKCa3.1. It increases the EC50 of Ca2+ on KCa2.3 channels from 0.36 to 1.2 microM. It also inhibits hERG with an IC50 of 71.8 microM and Kir3.1/Kir3.4 with an IC50 of 9.3 microM. |
| ln Vivo |
In isolated perfused rat hearts, AP14145 (10 μM) prolongs the atrial effective refractory period (AERP)[1]. In male sprague-dawley rats (250-350 g, 1-3 months old), AP14145 (2.5 and 5 mg/kg; bolus injections (iv)) prolongs the atrial effective refractory period[1]. The Cmax of AP14145 (5 mg/kg; bolus injections) in landrace pigs (their 30-35 kg gilts, aged 12–13 weeks) is 8355 nmol/L, and their t½ is 24.3 minutes [2].
In vivo, AP14145 (2.5 and 5 mg/kg; bolus injections (iv)) increases the duration of the atrial effective refractory period (AERP) in rats. It also reduces atrial fibrillation duration and prolongs atrial refractoriness without affecting the ventricular refractory period in an animal AF model. |
| Enzyme Assay |
For the SK channel assay, recombinant human SK2 or SK3 channels are expressed in HEK293 cells. Whole-cell patch-clamp recordings are performed, and AP14145 is applied in the bath solution. IC50 values are calculated based on the reduction in current amplitude.
|
| Cell Assay |
HEK293 cells stably expressing hKCa2.2 or hKCa2.3 channels are cultured in DMEM with 10% FBS. Whole-cell patch-clamp electrophysiology is performed. AP14145 hydrochloride is applied at varying concentrations (1 nM-30 uM), and the reduction in current is measured. IC50 values are determined from the dose-response curves.
|
| Animal Protocol |
In vivo, AP14145 is formulated in a suitable vehicle (e.g., 5% DMSO in saline) and administered to pigs or rats via intravenous bolus injection. Its effects on atrial refractoriness and fibrillation are assessed by electrophysiological mapping of the heart.
|
| ADME/Pharmacokinetics |
In pigs, AP14145 (5 mg/kg; bolus injections) has a Cmax of 8355 nmol/L and a half-life of 24.3 minutes. The compound is rapidly cleared, which aligns with its use for acute cardioversion rather than chronic maintenance.
|
| Toxicity/Toxicokinetics |
Specific toxicity data is limited. However, its off-target inhibition of hERG (IC50 = 71.8 microM) suggests a potential risk for QT prolongation at high concentrations, though the therapeutic window appears favorable due to the lower IC50 for the primary target.
|
| References |
[1]. Rafel Simó-Vicens, et al. A New Negative Allosteric Modulator, AP14145, for the Study of Small Conductance Calcium-Activated Potassium (KCa2) Channels. Br J Pharmacol. 2017 Dec;174(23):4396-4408.
[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. |
| Additional Infomation |
AP14145 hydrochloride is a research tool for studying the role of KCa2 channels in atrial fibrillation. It demonstrates antiarrhythmic effects in a Vernakalant-resistant porcine model of atrial fibrillation.
|
| Molecular Formula |
C18H18CLF3N4O
|
|---|---|
| Molecular Weight |
398.81
|
| Exact Mass |
398.112
|
| CAS # |
2387505-59-9
|
| PubChem CID |
146018940
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
501
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H](C1=CC(=CC=C1)C(F)(F)F)NC2=NC3=C(N2)C=CC=C3NC(=O)C.Cl
|
| InChi Key |
KGIUXIYNTCVBST-HNCPQSOCSA-N
|
| InChi Code |
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
|
| Chemical Name |
N-[2-[[(1R)-1-[3-(trifluoromethyl)phenyl]ethyl]amino]-1H-benzimidazol-4-yl]acetamide;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5075 mL | 12.5373 mL | 25.0746 mL | |
| 5 mM | 0.5015 mL | 2.5075 mL | 5.0149 mL | |
| 10 mM | 0.2507 mL | 1.2537 mL | 2.5075 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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