The Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK) pathway is considered the primary regulatory pathway for contraction of airway smooth muscle. ML-9 is a membrane-permeable organic substance that has been identified as an inhibitor of MLCK. ML-9 at a concentration of 30 or 100μM inhibited Ca2+ mobilization induced by a high concentration of K+, methacholine, and thapsigargin in guinea pig tracheal smooth muscle.[2] ML-9 at 30μM reduced the phosphorylation of Akt in lymph node carcinoma of the prostate (LNCaP) cells. Treatment with ML-9 (1 – 50μM, 2 – 24h) also dose- and time-dependently increased the expression level of LC3-II in LNCaP cells. Treatment of LNCaP cells with 30μM ML-9 for 24h significantly induced prostate cancer cell death.[1]
作用机制
ML-9 is a membrane-permeable organic substance that has been identified as an inhibitor of MLCK, Akt kinase, and stromal interaction molecule 1.[1]
ML-9 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human neutrophils
0–117 µM
1 hour
To evaluate the effect of ML-9 on intracellular calcium concentration in human neutrophils. Results showed that ML-9 enhanced the thapsigargin-induced increase in intracellular calcium levels, suggesting ML-9 may affect calcium flux through mechanisms other than SOCE.
To evaluate the inhibitory effects of ML-9 on SOCE and EYFP-Stim1 rearrangement. Results showed that ML-9 nearly completely inhibited SOCE and prevented the formation of punctate EYFP-Stim1 structures near the plasma membrane.
J Cell Sci. 2008 Mar 15;121(Pt 6):762-72.
HEK293 cells
7.8 µM (IC50)
5 seconds
ML-9 inhibits TRPC6 channels via a mechanism independent of MLCK activity, acting directly on the TRPC6 channel itself.
Br J Pharmacol. 2007 Sep;152(1):122-31.
3T3-L1 adipocytes
50 µM
90 minutes
To investigate the effect of ML-9 on metabolic stress and insulin-stimulated glucose uptake, results showed that ML-9 inhibited azide- and insulin-stimulated glucose uptake.
Biochem J. 1995 Aug 1;309 ( Pt 3)(Pt 3):731-6.
Clone9 cells
50 µM
90 minutes
To investigate the effect of ML-9 on metabolic stress and insulin-stimulated glucose uptake, results showed that ML-9 inhibited azide- and insulin-stimulated glucose uptake.
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