ML277 | CAS#1401242-74-7 | activator of KCNQ1

MedKoo Cat#: 555789 | Name: ML277

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

ML277

CAS#1401242-74-7

Theoretical Analysis

MedKoo Cat#: 555789

Name: ML277

CAS#: 1401242-74-7

Chemical Formula: C23H25N3O4S2

Exact Mass: 471.1286

Molecular Weight: 471.59

Elemental Analysis: C, 58.58; H, 5.34; N, 8.91; O, 13.57; S, 13.60

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,750.00	2 Weeks
2g	USD 5,950.00	2 Weeks

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Related CAS #

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Synonym

ML277; ML-277; ML 277; CID-53347902; CID 53347902; CID53347902; VU0458298-2; VU-0458298-2; VU 0458298-2; VU0458298-3;

IUPAC/Chemical Name

(2R)-N-[4-(4-Methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylphenyl)sulfonylpiperidine-2-carboxamide,

InChi Key

OXQNLLVUVDAEHC-OAQYLSRUSA-N

InChi Code

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

SMILES Code

O=C([C@@H]1N(S(=O)(C2=CC=C(C)C=C2)=O)CCCC1)NC3=NC(C4=CC=C(OC)C=C4)=CS3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

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.

Storage Condition

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

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

ML277 (CID-53347902) is a potent and selective activator of K(v)7.1 (KCNQ1) potassium channel activator (EC50=270 nM)

In vitro activity:

As previously described, there is a dramatic increase in peak current, a slowing of deactivation, and a loss of voltage-dependent gating upon exposure of KCNQ1 to 1 µM ML277 (Fig. 1; Yu et al., 2013, Xu et al., 2015). ML277 has profound effects on KCNQ1 single-channel kinetics, eliminating the flickering nature of the openings, converting them to discrete opening bursts, and increasing their amplitudes approximately threefold. Reference: J Gen Physiol. 2021 Dec 6;153(12):e202112969. https://pubmed.ncbi.nlm.nih.gov/34636894/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	50.5	107.17
	Ethanol	2.0	4.24

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 471.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Eldstrom J, McAfee DA, Dou Y, Wang Y, Fedida D. ML277 regulates KCNQ1 single-channel amplitudes and kinetics, modified by voltage sensor state. J Gen Physiol. 2021 Dec 6;153(12):e202112969. doi: 10.1085/jgp.202112969. Epub 2021 Oct 12. PMID: 34636894; PMCID: PMC8515649. 2. 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.

In vitro protocol:

In vivo protocol:

TBD

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.