| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
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.
| Targets |
IC50: 300 nM (MLCK)[1]
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 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].
ML-7 HCl rapidly and reversibly inhibited carbachol-induced cationic currents (ITRPC6) in HEK293 cells overexpressing murine TRPC6, with an efficacy slightly weaker than its congener ML-9. Conversely, ML-7 HCl caused rapid and reversible enhancement of currents arising from heterologously expressed TRPC7 channels (ITRPC7), whether constitutively active or activated by carbachol or the diacylglycerol analogue OAG. The inhibitory effect on TRPC6 and the enhancing effect on TRPC7 were both independent of myosin light chain kinase (MLCK) inhibition, as they were not prevented by MLCK inhibitory peptides or by co-expression of a dominant-negative MLCK mutant.[1] |
| 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].
|
| Cell Assay |
The effects of ML-7 HCl on TRPC6 and TRPC7 channels were assessed using whole-cell patch-clamp recordings in transfected HEK293 cells. Cells were voltage-clamped at -60 mV. Currents were elicited by extracellular application of carbachol (100 µM) or OAG (100 µM). Test compounds were applied via a fast solution exchange device. The extent of current modulation was calculated as the ratio of the current amplitude 5 seconds after drug application to that just before application.
Single-channel recordings of TRPC6 were performed in the inside-out patch configuration. The pipette solution contained carbachol (100 µM), tetraethylammonium (5 mM), and DIDS (100 µM) to suppress interfering currents. Bath application of ML-7 HCl (10 µM) rapidly reduced the activity of unitary TRPC6 channels (~35 pS). Inhibition was quantified as the ratio of mean current averaged over 2 seconds before and after drug application.[1] |
| References |
|
| Additional Infomation |
ML-7 HCl ([1-(5-iodonaphthalene-1-sulfonyl)piperazine, HCl]) is a membrane-permeable naphthalenesulfonamide derivative and a structural analog of ML-9, which is commonly used as a myosin light chain kinase (MLCK) inhibitor in cell studies. This study highlights that ML-7 HCl has a rapid, direct, and MLCK-independent regulatory effect on TRPC channels: inhibiting TRPC6 and enhancing TRPC7 activity. This nonspecificity suggests that caution should be exercised when interpreting functional studies that rely solely on this compound to infer MLCK activity. [1]
|
| 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
|
|
| Related CAS # |
|
|
| 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]
|
|
| 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
|
|
| Chemical Name |
|
|
| Synonyms |
|
|
| 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. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Effects of ML-9 and ML-7 on single TRPC6 channels.Br J Pharmacol.2007 Sep;152(1):122-31. |
Activation mode of TRPC6 did not affect the efficacy of ML-9 and ML-7. |
Enhancing actions of ML-compounds on macroscopic TRPC7 current (ITRPC7). Conventional whole-cell recording at −60 mV with Ca2+-free external solution.Br J Pharmacol.2007 Sep;152(1):122-31. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
