ML-7 hydrochloride (HCl), a novel naphthalene sulphonamide derivative, is a novel potent inhibitor of Myosin light chain kinase (MLCK) with anticancer effects. It exhibits IC50 of 300 nM and IC50>10 μM for MLCK and TRPC6 channel respectively. Myosin light chain kinase (MLCK) plays a pivotal role in regulation of cellular functions, the evidence often relying on the effects of extracelluarly administered drugs such as ML-9. ML-7 exerts non-specific inhibitory actions on the TRPC6 channel, a transient receptor potential (TRP) protein.
Physicochemical Properties
| Molecular Formula | C15H18CLIN2O2S.H2O | |
| Molecular Weight | 452.7381 | |
| Exact Mass | 451.982 | |
| Elemental Analysis | C, 39.79; H, 4.01; Cl, 7.83; I, 28.03; N, 6.19; O, 7.07; S, 7.08 | |
| CAS # | 110448-33-4 | |
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| PubChem CID | 9803932 | |
| Appearance | Light yellow to yellow solid powder | |
| Boiling Point | 542.7ºC at 760 mmHg | |
| Melting Point | 246-249ºC dec. | |
| Flash Point | 282ºC | |
| LogP | 4.577 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 22 | |
| Complexity | 451 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | IC1=C([H])C([H])=C([H])C2=C1C([H])=C([H])C([H])=C2S(N1C([H])([H])C([H])([H])N([H])C([H])([H])C([H])([H])C1([H])[H])(=O)=O.Cl[H] |
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| InChi Key | KDDALCDYHZIZMH-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C15H17IN2O2S.ClH/c16-14-6-1-5-13-12(14)4-2-7-15(13)21(19,20)18-10-3-8-17-9-11-18;/h1-2,4-7,17H,3,8-11H2;1H | |
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| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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
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| ln Vitro | With an IC50 of 0.8 μM, ML-7 hydrochloride inhibits rabbit portal α1-adrenoceptor NSCC[1]. In addition, the myosin light chain kinase (MLCK) inhibitor ML-7 hydrochloride (3 μM, 10 μM) reduced the contraction generated by dexmedetomidine (DMT) (p<0.05 in comparison to the control) [2]. | |
| ln Vivo | The ML-7 hydrochloride and vehicle groups did not exhibit different levels of Evans blue extravasation in sham-operated animals (sham+vehicle: 0.26±0.02 OD/g; sham+ML-7 hydrochloride: 0.26±0.02 OD/g). Evans blue levels in the brain were significantly lower in mice treated with CCI than in animals treated with vehicle (CCI+vehicle: 0.42±0.04 OD/g; CCI+ML-7 hydrochloride: 0.35±0.05 OD/g, p =0.048) following MLCK inhibition with ML-7 hydrochloride[3]. | |
| References |
[1]. Myosin light chain kinase-independent inhibition by ML-9 of murine TRPC6 channels expressed in HEK293cells. Br J Pharmacol. 2007 Sep;152(1):122-31. [2]. Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation. Int J Med Sci. 2015 Sep 4;12(9):727-36. [3]. Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury. J Neurochem. 2010 Feb;112(4):1015-25. [4]. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics. 2020 Feb 18;10(8):3622-3635. |
Solubility Data
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.69 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 16.7 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 | 2.2088 mL | 11.0439 mL | 22.0877 mL | |
| 5 mM | 0.4418 mL | 2.2088 mL | 4.4175 mL | |
| 10 mM | 0.2209 mL | 1.1044 mL | 2.2088 mL |