ML418 is a selective and brain-penetrant pore blocker of Kir7.1 potassium channel (IC50, 310 nM). 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.
Physicochemical Properties
| Molecular Formula | C19H24CLN3O3 |
| Molecular Weight | 377.865163803101 |
| Exact Mass | 377.15 |
| CAS # | 1928763-08-9 |
| Related CAS # | 1928763-08-9; |
| PubChem CID | 91667465 |
| Appearance | White to off-white solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 26 |
| Complexity | 471 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1C2=CC=CN=C2C(=C(C=1)CN1CCC(CC1)NC(=O)OC(C)C)O |
| 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) |
| Chemical Name | iso-Propyl (1-((5-chloro-8-hydroxyquinolin-7-yl)methyl)piperidin-4-yl)carbamate |
| Synonyms | ML418 ML-418 ML 418 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | ML418 exhibits inhibitory activity against Kir7.1 that is dose-dependent, with an IC50 value of 0.31 μM [1]. With IC50 values of 1.3 μM and 1.9 μM, respectively, ML418 exhibits selectivity towards Kir7.1 and Kir6.2/SUR1[1]. |
| ln Vivo | ML418 (ip; 30 mg/kg) has good CNS distribution, good CNS permeability, and a strong PK impact [1]. |
| Animal Protocol |
Animal/Disease Models: Rat and mouse[1] Doses: 30 mg/kg Route of Administration: intraperitoneal Experimental Results: demonstrated a suitable PK curve (Cmax = 0.20 μM, Tmax = 3 hrs (hrs (hours))) on the central nervous system of mouse brain Systemic permeability is excellent: Kp is 10.9, brain (323.9 ng/g): plasma (29.5 ng/mL). |
| References |
[1]. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. ACS Chem Neurosci. 2016 Jul 20;7(7):1013-23. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~20.83 mg/mL (~55.12 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6464 mL | 13.2321 mL | 26.4641 mL | |
| 5 mM | 0.5293 mL | 2.6464 mL | 5.2928 mL | |
| 10 mM | 0.2646 mL | 1.3232 mL | 2.6464 mL |