ML418 | CAS#1928763-08-9 | blocker of Kir7.1 potassium channels

MedKoo Cat#: 561419 | Name: ML418

Description:

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

ML418 is a selective, sub-micromolar pore blocker of Kir7.1 potassium channels. The inward rectifier potassium (Kir) channel Kir7.1 (KCNJ13) is a key regulator of melanocortin signaling in the brain, electrolyte homeostasis in the eye, and uterine muscle contractility during pregnancy.

Chemical Structure

ML418

CAS#1928763-08-9

Theoretical Analysis

MedKoo Cat#: 561419

Name: ML418

CAS#: 1928763-08-9

Chemical Formula: C19H24ClN3O3

Exact Mass: 377.1506

Molecular Weight: 377.87

Elemental Analysis: C, 60.39; H, 6.40; Cl, 9.38; N, 11.12; O, 12.70

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,450.00	2 Weeks
500mg	USD 2,250.00	2 Weeks
1g	USD 3,250.00	2 Weeks
2g	USD 5,850.00	2 Weeks

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Related CAS #

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Synonym

ML418; ML-418; ML 418;

IUPAC/Chemical Name

iso-Propyl (1-((5-chloro-8-hydroxyquinolin-7-yl)methyl)piperidin-4-yl)carbamate

InChi Key

CWIXCQOSULUGBT-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H24ClN3O3/c1-12(2)26-19(25)22-14-5-8-23(9-6-14)11-13-10-16(20)15-4-3-7-21-17(15)18(13)24/h3-4,7,10,12,14,24H,5-6,8-9,11H2,1-2H3,(H,22,25)

SMILES Code

O=C(OC(C)C)NC1CCN(CC2=CC(Cl)=C3C=CC=NC3=C2O)CC1

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

>2 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:

ML418 is a potent, selective and CNS penetrating Kir7.1 potassium channel blocker. ML418 inhibits Kir7.1 with an IC50 value of 0.31 μM.

In vitro activity:

Lead optimization with medicinal chemistry generated ML418, which exhibits sub-micromolar activity (IC50 = 310 nM) and superior selectivity over other Kir channels (at least 17-fold selective over Kir1.1, Kir2.1, Kir2.2, Kir2.3, Kir3.1/3.2, and Kir4.1) except for Kir6.2/SUR1 (equally potent). Evaluation in the EuroFins Lead Profiling panel of 64 GPCRs, ion-channels, and transporters for off-target activity of ML418 revealed a relatively clean ancillary pharmacology. While ML418 exhibited low CLHEP in human microsomes which could be modulated with lipophilicity adjustments, it showed high CLHEP in rat microsomes regardless of lipophilicity. Reference: ACS Chem Neurosci. 2016 Jul 20;7(7):1013-23. https://pubmed.ncbi.nlm.nih.gov/27184474/

In vivo activity:

To investigate whether inhibition of the Kir7.1 channel would affect the mechanical sensitivity, ML418 (30 mg/kg, i.p.), the first selective blocker of Kir7.1 channel was administered for consecutive 5 days. As shown in Figure 2A, the PWTs were significantly decreased in the ML418‐treated group as compared to the naïve or vehicle group. Furthermore, this study observed the effect of Kir7.1 knockdown in dorsal horn on pain sensitivity by Kir7.1 siRNA (1 nmol/10 μl, i.t.) for 10 consecutive days in naive rats. Reference: CNS Neurosci Ther. 2022 Aug;28(8):1259-1267. https://pubmed.ncbi.nlm.nih.gov/35633059/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	14.2	37.57

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 377.87 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. Swale DR, Kurata H, Kharade SV, Sheehan J, Raphemot R, Voigtritter KR, Figueroa EE, Meiler J, Blobaum AL, Lindsley CW, Hopkins CR, Denton JS. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. ACS Chem Neurosci. 2016 Jul 20;7(7):1013-23. doi: 10.1021/acschemneuro.6b00111. Epub 2016 May 24. PMID: 27184474; PMCID: PMC5131535. 2. Lv YY, Wang H, Fan HT, Xu T, Xin WJ, Guo RX. SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons. CNS Neurosci Ther. 2022 Aug;28(8):1259-1267. doi: 10.1111/cns.13871. Epub 2022 May 27. PMID: 35633059; PMCID: PMC9253747.

In vitro protocol:

In vivo protocol:

1. Lv YY, Wang H, Fan HT, Xu T, Xin WJ, Guo RX. SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons. CNS Neurosci Ther. 2022 Aug;28(8):1259-1267. doi: 10.1111/cns.13871. Epub 2022 May 27. PMID: 35633059; PMCID: PMC9253747.

1: Kharade SV, Sheehan JH, Figueroa EE, Meiler J, Denton JS. Pore Polarity and Charge Determine Differential Block of Kir1.1 and Kir7.1 Potassium Channels by Small-Molecule Inhibitor VU590. Mol Pharmacol. 2017 Sep;92(3):338-346. doi: 10.1124/mol.117.108472. Epub 2017 Jun 15. PubMed PMID: 28619748; PubMed Central PMCID: PMC5553192. 2: Swale DR, Kurata H, Kharade SV, Sheehan J, Raphemot R, Voigtritter KR, Figueroa EE, Meiler J, Blobaum AL, Lindsley CW, Hopkins CR, Denton JS. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. ACS Chem Neurosci. 2016 Jul 20;7(7):1013-23. doi: 10.1021/acschemneuro.6b00111. Epub 2016 May 24. PubMed PMID: 27184474; PubMed Central PMCID: PMC5131535.