ML277 | Potent Kv7.1 activator

ML277 chemical structure Focus Biomolecules

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ML277 (1401242-74-7) is a potent (EC50 = 260 nM) activator of Kv7.1 with selectivity against Kv7.2, Kv7.4, and Kv11.1 (hERG).1 ML277 enhances cardiac delayed rectifier K+ currents (IKs) in human iPSC-derived cardiomyocytes from normal and long QT-interval syndrome afflicted patients suggesting potential therapeutic use in long QT-interval syndrome.2,3 It displayed cardioprotective effects against ischemia in cellular and whole-heart models.4

References/Citations:

  1. Mattman et al. (2012) Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent, and selective K(v)7.1(KCNQ1 potassium channel activator; Bioorg. Med. Chem. Lett. 22 5936
  2. Yu et al. (2013) Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels; Proc. Nat. Acad. Sci. USA 110 8732
  3. Ma et al. (2015) Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes; Stem Cell Res. Ther. 6 39
  4. Brennan et al. (2023) Slowly activating voltage-gated potassium current potentiation by ML277 is a novel cardioprotective intervention; PNAS Nexus 2 pgad156
1401242-74-7, Kv7.1 activator, ML 277, ML277, ML277 supplier

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ML277 (1401242-74-7) is a potent (EC50 = 260 nM) activator of Kv7.1 with selectivity against Kv7.2, Kv7.4, and Kv11.1 (hERG).1 ML277 enhances cardiac delayed rectifier K+ currents (IKs) in human iPSC-derived cardiomyocytes from normal and long QT-interval syndrome afflicted patients suggesting potential therapeutic use in long QT-interval syndrome.2,3 It displayed cardioprotective effects against ischemia in cellular and whole-heart models.4

References/Citations:

  1. Mattman et al. (2012) Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent, and selective K(v)7.1(KCNQ1 potassium channel activator; Bioorg. Med. Chem. Lett. 22 5936
  2. Yu et al. (2013) Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels; Proc. Nat. Acad. Sci. USA 110 8732
  3. Ma et al. (2015) Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes; Stem Cell Res. Ther. 6 39
  4. Brennan et al. (2023) Slowly activating voltage-gated potassium current potentiation by ML277 is a novel cardioprotective intervention; PNAS Nexus 2 pgad156