ML277
ML277 is a potent activator of KCNQ1 (Kv7.1) channels with >100-fold selectivity versus KCNQ2 and KCNQ4 and no activity against the hERG potassium channel up to 30 μM. KCNQ1 is a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. ML277 is the first selective and potent activator found, with an EC50 of 260 nM.
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Chemical Information
| Name | ML277 |
|---|---|
| Iupac Chemical Name | (2R)-N-[4-(4-Methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylphenyl)sulfonylpiperidine-2-carboxamide, |
| Synonyms | ML277; ML-277; ML 277; CID-53347902; CID 53347902; CID53347902; VU0458298-2; VU-0458298-2; VU 0458298-2; VU0458298-3; |
| Molecular Formula | C23H25N3O4S2 |
| Molecular Weight | 471.59 |
| Smile | O=C([C@@H]1N(S(=O)(C2=CC=C(C)C=C2)=O)CCCC1)NC3=NC(C4=CC=C(OC)C=C4)=CS3 |
| InChiKey | OXQNLLVUVDAEHC-OAQYLSRUSA-N |
| InChi | InChI=1S/C23H25N3O4S2/c1-16-6-12-19(13-7-16)32(28,29)26-14-4-3-5-21(26)22(27)25-23-24-20(15-31-23)17-8-10-18(30-2)11-9-17/h6-13,15,21H,3-5,14H2,1-2H3,(H,24,25,27)/t21-/m1/s1 |
| CAS Number | 1401242-74-7 |
| Related CAS |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Solubility | Soluble in DMSO |
| Handling | |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| HS Code |
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| Mechanism | |
| Cell study | |
| Animal study | |
| Clinical study |
1: Hou P, Shi J, White KM, Gao Y, Cui J. ML277 specifically enhances the fully activated open state of KCNQ1 by modulating VSD-pore coupling. Elife. 2019 Jul 22;8:e48576. doi: 10.7554/eLife.48576. PMID: 31329101; PMCID: PMC6684268.
2: Kanaporis G, Kalik ZM, Blatter LA. Action potential shortening rescues atrial calcium alternans. J Physiol. 2019 Feb;597(3):723-740. doi: 10.1113/JP277188. Epub 2018 Dec 5. PMID: 30412286; PMCID: PMC6355632.
3: Wei X, Zhang Y, Yin B, Wen J, Cheng J, Fu X. The expression and function of KCNQ potassium channels in human chorionic plate arteries from women with normal pregnancies and pre-eclampsia. PLoS One. 2018 Mar 26;13(3):e0192122. doi: 10.1371/journal.pone.0192122. PMID: 29579054; PMCID: PMC5868761.
4: López-Hermoso C, de la Haba RR, Sánchez-Porro C, Ventosa A. Salinivibrio kushneri sp. nov., a moderately halophilic bacterium isolated from salterns. Syst Appl Microbiol. 2018 May;41(3):159-166. doi: 10.1016/j.syapm.2017.12.001. Epub 2017 Dec 21. PMID: 29331569.
5: Tsvetkov D, Kaßmann M, Tano JY, Chen L, Schleifenbaum J, Voelkl J, Lang F, Huang Y, Gollasch M. Do KV 7.1 channels contribute to control of arterial vascular tone? Br J Pharmacol. 2017 Jan;174(2):150-162. doi: 10.1111/bph.13665. Epub 2016 Dec 20. PMID: 28000293; PMCID: PMC5192887.
6: Kuusela J, Kim J, Räsänen E, Aalto-Setälä K. The Effects of Pharmacological Compounds on Beat Rate Variations in Human Long QT-Syndrome Cardiomyocytes. Stem Cell Rev Rep. 2016 Dec;12(6):698-707. doi: 10.1007/s12015-016-9686-0. PMID: 27646833; PMCID: PMC5106508.
7: Ma D, Wei H, Lu J, Huang D, Liu Z, Loh LJ, Islam O, Liew R, Shim W, Cook SA. 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. 2015 Mar 19;6(1):39. doi: 10.1186/s13287-015-0027-z. PMID: 25889101; PMCID: PMC4396080.
8: Svalø J, Sheykhzade M, Nordling J, Matras C, Bouchelouche P. Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction. PLoS One. 2015 Feb 18;10(2):e0117350. doi: 10.1371/journal.pone.0117350. PMID: 25692982; PMCID: PMC4333569.
9: Xu Y, Wang Y, Zhang M, Jiang M, Rosenhouse-Dantsker A, Wassenaar T, Tseng GN. Probing binding sites and mechanisms of action of an I(Ks) activator by computations and experiments. Biophys J. 2015 Jan 6;108(1):62-75. doi: 10.1016/j.bpj.2014.10.059. PMID: 25564853; PMCID: PMC4286593.
10: Yu H, Lin Z, Mattmann ME, Zou B, Terrenoire C, Zhang H, Wu M, McManus OB, Kass RS, Lindsley CW, Hopkins CR, Li M. Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8732-7. doi: 10.1073/pnas.1300684110. Epub 2013 May 6. PMID: 23650380; PMCID: PMC3666726.
11: Yu H, Lin Z, Xu K, Huang X, Long S, Wu M, McManus OB, Le Engers J, Mattmann ME, Engers DW, Le UM, Lindsley CW, Hopkins CR, Li M. Identification of a novel, small molecule activator of KCNQ1 channels. 2011 Dec 16 [updated 2013 Mar 7]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 23762928.
12: Mattmann ME, Yu H, Lin Z, Xu K, Huang X, Long S, Wu M, McManus OB, Engers DW, Le UM, Li M, Lindsley CW, Hopkins CR. 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. 2012 Sep 15;22(18):5936-41. doi: 10.1016/j.bmcl.2012.07.060. Epub 2012 Aug 2. PMID: 22910039; PMCID: PMC3433560.
Chemical Structure
