WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 530537
CAS#: 110448-33-4
Description: ML-7 is a MLCK inhibitor. ML-7 inhibits smooth muscle myosin light chain kinase (MLCK) with a Ki value of 0.3 µM. ML-7 amplifies the quinocetone-induced cell death through akt and MAPK-mediated apoptosis on HepG2 cell line. ML-7 inhibits exocytosis of superoxide-producing intracellular compartments in human neutrophils stimulated with phorbol myristate acetate in a myosin light chain kinase-independent manner.
MedKoo Cat#: 530537
Name: ML-7 HCl
CAS#: 110448-33-4
Chemical Formula: C15H18ClIN2O2S
Exact Mass:
Molecular Weight: 452.7355
Elemental Analysis: C, 39.79; H, 4.01; Cl, 7.83; I, 28.03; N, 6.19; O, 7.07; S, 7.08
Synonym: ML-7 HCl; ML-7 hydrochloride; ML-7; ML 7; ML7.
IUPAC/Chemical Name: hexahydro-1-[(5-iodo-1-naphthalenyl)sulfonyl]-1H-1,4-diazepine, monohydrochloride
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
SMILES Code: O=S(N1CCNCCC1)(C2=C3C=CC=C(I)C3=CC=C2)=O.[H]Cl
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
| Biological target: | ML-7 hydrochloride is a naphthalene sulphonamide derivative, potently inhibits MLCK (IC50=300 nM). |
| In vitro activity: | TBD |
| In vivo activity: | These symptoms of AS (atherosclerosis) were significantly improved following treatment with ML7, as demonstrated in the ML7 group. Hematoxylin & eosin and immunohistochemical staining indicated that ML7 was able to decrease the expression of MLCK and MLC phosphorylation in the arterial wall of rabbits fed a high‑fat diet. Reference: Mol Med Rep. 2015 Sep;12(3):4109-4116. https://pubmed.ncbi.nlm.nih.gov/26096176/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 66.26 | |
| DMSO | 46.41 | 102.51 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.1 | |
| Ethanol | 1.0 | 2.21 | |
| Water | 1.43 | 3.16 |
The following data is based on the product molecular weight 452.7355 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. Cheng X, Wang X, Wan Y, Zhou Q, Zhu H, Wang Y. Myosin light chain kinase inhibitor ML7 improves vascular endothelial dysfunction via tight junction regulation in a rabbit model of atherosclerosis. Mol Med Rep. 2015 Sep;12(3):4109-4116. doi: 10.3892/mmr.2015.3973. Epub 2015 Jun 22. PMID: 26096176; PMCID: PMC4526030. 2. Luh C, Kuhlmann CR, Ackermann B, Timaru-Kast R, Luhmann HJ, Behl C, Werner C, Engelhard K, Thal SC. Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury. J Neurochem. 2010 Feb;112(4):1015-25. doi: 10.1111/j.1471-4159.2009.06514.x. Epub 2009 Nov 27. PMID: 19943851. |
| In vitro protocol: | TBD |
| In vivo protocol: | 1. Cheng X, Wang X, Wan Y, Zhou Q, Zhu H, Wang Y. Myosin light chain kinase inhibitor ML7 improves vascular endothelial dysfunction via tight junction regulation in a rabbit model of atherosclerosis. Mol Med Rep. 2015 Sep;12(3):4109-4116. doi: 10.3892/mmr.2015.3973. Epub 2015 Jun 22. PMID: 26096176; PMCID: PMC4526030. 2. Luh C, Kuhlmann CR, Ackermann B, Timaru-Kast R, Luhmann HJ, Behl C, Werner C, Engelhard K, Thal SC. Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury. J Neurochem. 2010 Feb;112(4):1015-25. doi: 10.1111/j.1471-4159.2009.06514.x. Epub 2009 Nov 27. PMID: 19943851. |
1: Zhou Y, Zhang S, Deng S, Dai C, Tang S, Yang X, Li D, Zhao K, Xiao X. ML-7 amplifies the quinocetone-induced cell death through akt and MAPK-mediated apoptosis on HepG2 cell line. Toxicol Mech Methods. 2016;26(1):11-21. doi: 10.3109/15376516.2015.1090513. PubMed PMID: 26446980.
2: Cherlet M, Gleich S, Dewerchin H, Nauwynck H, Daminet S, De Backer P, Croubels S. Quantitative analysis of an anti-viral immune escape compound ML-7 in feline plasma using ultra performance liquid chromatography/electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Sep 15;905:118-26. doi: 10.1016/j.jchromb.2012.08.014. PubMed PMID: 22925719.
3: Lin HB, Cadete VJ, Sawicka J, Wozniak M, Sawicki G. Effect of the myosin light chain kinase inhibitor ML-7 on the proteome of hearts subjected to ischemia-reperfusion injury. J Proteomics. 2012 Sep 18;75(17):5386-95. doi: 10.1016/j.jprot.2012.06.016. PubMed PMID: 22749930.
4: Rosenthal R, Choritz L, Schlott S, Bechrakis NE, Jaroszewski J, Wiederholt M, Thieme H. Effects of ML-7 and Y-27632 on carbachol- and endothelin-1-induced contraction of bovine trabecular meshwork. Exp Eye Res. 2005 Jun;80(6):837-45. PubMed PMID: 15939040.
5: Odani K, Kobayashi T, Ogawa Y, Yoshida S, Seguchi H. ML-7 inhibits exocytosis of superoxide-producing intracellular compartments in human neutrophils stimulated with phorbol myristate acetate in a myosin light chain kinase-independent manner. Histochem Cell Biol. 2003 May;119(5):363-70. PubMed PMID: 12750906.
6: Kelley SJ, Thomas R, Dunham PB. Candidate inhibitor of the volume-sensitive kinase regulating K-Cl cotransport: the myosin light chain kinase inhibitor ML-7. J Membr Biol. 2000 Nov 1;178(1):31-41. PubMed PMID: 11058685.
7: Kozgunova E, Higashiyama T, Kurihara D. Cytokinesis defect in BY-2 cells caused by ATP-competitive kinase inhibitors. Plant Signal Behav. 2016 Oct 2;11(10):e1238547. PubMed PMID: 27662076; PubMed Central PMCID: PMC5257169.
8: Zhang Y, Li J, Chi Y, Li M, Pan X, Zhang Q, He X, Liu Y. [Myosin light chain kinase involved in change of intestinal mucosal barrier function in nonalcoholic steatohepatitis mice model]. Zhonghua Nei Ke Za Zhi. 2015 May;54(5):434-8. Chinese. PubMed PMID: 26080824.
9: Tian B, Brumback LC, Kaufman PL. ML-7, chelerythrine and phorbol ester increase outflow facility in the monkey Eye. Exp Eye Res. 2000 Dec;71(6):551-66. PubMed PMID: 11095907.
10: Shi W, Xu C, Hussain M, Wu F, Lu M, Wu X, Tang L, Wu X, Wu J. Inhibition of Myosin Light-Chain Kinase Enhances the Clearance of Lipopolysaccharide-Induced Lung Inflammation Possibly by Accelerating Neutrophil Apoptosis. Shock. 2017 Mar 7. doi: 10.1097/SHK.0000000000000863. [Epub ahead of print] PubMed PMID: 28272166.
11: Natarajan P, Crothers JM Jr, Rosen JE, Nakada SL, Rakholia M, Okamoto CT, Forte JG, Machen TE. Myosin IIB and F-actin control apical vacuolar morphology and histamine-induced trafficking of H-K-ATPase-containing tubulovesicles in gastric parietal cells. Am J Physiol Gastrointest Liver Physiol. 2014 Apr 15;306(8):G699-710. doi: 10.1152/ajpgi.00316.2013. PubMed PMID: 24578340; PubMed Central PMCID: PMC3989701.
12: Rossi JL, Todd T, Bazan NG, Belayev L. Inhibition of Myosin light-chain kinase attenuates cerebral edema after traumatic brain injury in postnatal mice. J Neurotrauma. 2013 Oct 1;30(19):1672-9. doi: 10.1089/neu.2013.2898. PubMed PMID: 23984869; PubMed Central PMCID: PMC3787387.
13: Bil-Lula I, Lin HB, Biały D, Wawrzyńska M, Diebel L, Sawicka J, Woźniak M, Sawicki G. Subthreshold nitric oxide synthase inhibition improves synergistic effects of subthreshold MMP-2/MLCK-mediated cardiomyocyte protection from hypoxic injury. J Cell Mol Med. 2016 Jun;20(6):1086-94. doi: 10.1111/jcmm.12827. PubMed PMID: 26992120; PubMed Central PMCID: PMC4882990.
14: Mackenzie AC, Kyle DD, McGinnis LA, Lee HJ, Aldana N, Robinson DN, Evans JP. Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging: implications for functional defects in aged eggs. Mol Hum Reprod. 2016 Jun;22(6):397-409. doi: 10.1093/molehr/gaw019. PubMed PMID: 26921397; PubMed Central PMCID: PMC4884917.
15: Wang B, Yan Y, Zhou J, Zhou Q, Gui S, Wang Y. A novel all-trans retinoid acid derivatives inhibits the migration of breast cancer cell lines MDA-MB-231 via myosin light chain kinase involving p38-MAPK pathway. Biomed Pharmacother. 2013 Jun;67(5):357-62. doi: 10.1016/j.biopha.2013.03.016. PubMed PMID: 23602051.
16: Eikemo H, Moltzau LR, Hussain RI, Nguyen CH, Qvigstad E, Levy FO, Skomedal T, Osnes JB. CaMKII in addition to MLCK contributes to phosphorylation of regulatory light chain in cardiomyocytes. Biochem Biophys Res Commun. 2016 Feb 26;471(1):219-25. doi: 10.1016/j.bbrc.2016.01.132. PubMed PMID: 26809094.
17: Droy-Lefaix MT, Bueno L, Caron P, Belot E, Roche O. Ocular inflammation and corneal permeability alteration by benzalkonium chloride in rats: a protective effect of a myosin light chain kinase inhibitor. Invest Ophthalmol Vis Sci. 2013 Apr 17;54(4):2705-10. doi: 10.1167/iovs.12-10193. PubMed PMID: 23518768; PubMed Central PMCID: PMC3632265.
18: Liu X, Xu J, Mei Q, Han L, Huang J. Myosin light chain kinase inhibitor inhibits dextran sulfate sodium-induced colitis in mice. Dig Dis Sci. 2013 Jan;58(1):107-14. doi: 10.1007/s10620-012-2304-3. PubMed PMID: 22777616.
19: Wu F, Guo X, Xu J, Wang W, Li B, Huang Q, Su L, Xu Q. Role of myosin light chain and myosin light chain kinase in advanced glycation end product-induced endothelial hyperpermeability in vitro and in vivo. Diab Vasc Dis Res. 2016 Mar;13(2):137-44. doi: 10.1177/1479164115610469. PubMed PMID: 26607798.
20: Nepiyushchikh ZV, Chakraborty S, Wang W, Davis MJ, Zawieja DC, Muthuchamy M. Differential effects of myosin light chain kinase inhibition on contractility, force development and myosin light chain 20 phosphorylation of rat cervical and thoracic duct lymphatics. J Physiol. 2011 Nov 15;589(Pt 22):5415-29. doi: 10.1113/jphysiol.2011.218446. PubMed PMID: 21930597; PubMed Central PMCID: PMC3240881.
