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A-935142 CAS: 1031335-85-9

Category: Inhibitors
Product Name: A-935142
Cat No: I000328
CAS No: 1031335-85-9
Synonyms: A-935142;2-[4-[4-[5-(trifluoromethyl)-1H-pyrazol-3-yl]phenyl]cyclohexyl]acetic acid
Molecular Formula: C18H19F3N2O2
Molecular Weight: 352.3572
InChI: InChI=1S/C18H19F3N2O2/c19-18(20,21)16-10-15(22-23-16)14-7-5-13(6-8-14)12-3-1-11(2-4-12)9-17(24)25/h5-8,10-12H,1-4,9H2,(H,22,23)(H,24,25)
Solubility: Soluble in DMSO
Target: None
CAS 1031335-85-9,A-935142
  • Description

A-935142 is a novel hERG channel activator.

  • Spec

Appearance:Solid powder
Purity: > 98%

  • References

1:Life Sci. 2012 Apr 20;90(15-16):607-11. doi: 10.1016/j.lfs.2012.02.017. Epub 2012 Mar 3. Characterization of A-935142, a hERG enhancer, in the presence and absence of standard hERG blockers.Liu X,Limberis JT,Su Z,Houseman K,Diaz GJ,Gintant GA,Cox BF,Martin RL, PMID: 22406079 DOI: 10.1016/j.lfs.2012.02.017
Abstract: AIMS: In a previous study we found that A-935142 enhanced hERG current in a concentration-dependent manner by facilitating activation, reducing inactivation, and slowing deactivation (Su et al., 2009). A-935142 also shortened action potential duration (APD90) in canine Purkinje fibers and guinea pig atrial tissue. This study focused on the combined effects of the prototypical hERG enhancer, A-935142 and two hERG current blockers (sotalol and terfenadine).MAIN METHODS: The whole-cell voltage clamp method with HEK 293 cells heterologously expressing the hERG channel (Kv 11.1) was used.KEY FINDINGS: A-935142 did not compete with 3H-dofetilide binding, suggesting that A-935142 does not overlap the binding site of typical hERG blockers. In whole-cell voltage clamp studies we found: 1) 60 μM A-935142 enhanced hERG current in the presence of 150 μM sotalol (57.5±5.8%) to a similar extent as seen with A-935142 alone (55.6±5.1%); 2) 150 μM sotalol blocked hERG current in the presence of 60 μM A-935142 (43.5±1.5%) to a similar extent as that seen with sotalol alone (42.0±3.2%) and 3) during co-application, hERG current enhancement was followed by current blockade. Similar results were obtained with 60 nM terfenadine combined with A-935142.SIGNIFICANCE: These results suggest that the hERG enhancer, A-935142 does not compete with these two known hERG blockers at their binding site within the hERG channel. This selective hERG current enhancement may be useful as a treatment for inherited or acquired LQTS (Casis et al., 2006).Copyright © 2012 Elsevier Inc. All rights reserved.

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