W-7 hydrochloride selectively antagonizes calmodulin. It hinders both the Ca2+-calmodulin-dependent phosphodiesterase and the myosin light chain kinase, exhibiting IC50 values of 28 μM for the former and 51 μM for the latter[1][2]. W-7 hydrochloride is known to induce apoptosis and possesses antitumor properties[3]. Predominantly located in the cytoplasm, W-7 hydrochloride suppresses the proliferation of CHO-K1 cells. It specifically impedes the cell cycle at the G1/S boundary phase, with 25 μM of W-7 hydrochloride halting cell growth at this stage[1]. At a concentration of 100 μM, W-7 displays comparable antagonistic effects on the contractile reactions to both carbachol and KCl. W-7 also inhibits the rise in phosphorylated myosin light chain (P-LC) levels that is typically observed following a 1-minute exposure to 10 μM carbachol. This inhibition by W-7 ultimately counteracts smooth muscle contraction by preventing the initial surge in P-LC phosphorylation[2]. Administering W-7 leads to a dose-responsive curtailment of cell growth across various human multiple myeloma cell lines. It prompts G1 phase arrest in the cell cycle by diminishing cyclins and elevating p21cip1 levels. Furthermore, W-7 triggers apoptosis through the activation of caspases, a process that is partially attributed to the increase in intracellular calcium and the depolarization of the mitochondrial membrane potential, as well as the inhibition of STAT3 phosphorylation, which results in the reduced expression of the Mcl-1 protein[3].
W-7 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human embryonic kidney (HEK) 293 cells
13.4 µM
10 minutes
The hKIR2.1 current was significantly inhibited by W-7 at test potentials of -120 to -80 mV and -60 to -10 mV.
Br J Pharmacol. 2010 Oct;161(4):872-84
Human embryonic kidney (HEK) 293 cells
6.5 µM
10 minutes
W-7 significantly suppressed activity of hKv1.5 channels at test potentials of 0 to +50 mV.
Br J Pharmacol. 2010 Oct;161(4):872-84
Human embryonic kidney (HEK) 293 cells
3.5 µM
10 minutes
W-7 decreased the hERG current (IhERG) in a concentration-dependent manner (IC50: 3.5 μM), and the inhibition was more significant at depolarization potentials between +10 and +60 mV.
Br J Pharmacol. 2010 Oct;161(4):872-84
Human adherent monocytes
5 µM and 10 µM
12 hours
To investigate the effect of W-7 on PT- and LPS-induced IL-1 production. Results showed that W-7 significantly suppressed PT-induced IL-1 production but had no significant effect on LPS-induced IL-1 production.
Immunology. 1989 Jun;67(2):210-5
Vascular smooth muscle cells
100 µM
30 minutes
Inhibited AngII-induced ERK1/2 phosphorylation
Biochem Pharmacol. 2018 Jun;152:187-200
Cochlear outer hair cells (OHCs)
150 µM
30–60 minutes
W-7 shifted the voltage sensitivity of the membrane capacitance in the depolarised direction
J Physiol. 2001 Mar 15;531(Pt 3):667-76
W-7 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
FVB/NJ mice
HSOD1G93A transgenic mouse model
Oral gavage
100 mg/kg
Once daily, starting at disease onset (90 days of age) until end stage
PCA significantly extended survival, improved motor function, diminished gliosis in the spinal cord, protected spinal motor neurons, and sustained neuromuscular junctions in the hSOD1G93A mouse model of ALS.
Front Plant Sci. 2018 Sep 3;9:1284
W-7 HCl 动物研究
Animal study
Treatment with W-7, administered at 3 mg/kg through intraperitoneal injection over five consecutive days each week, markedly diminishes tumor development in a murine multiple myeloma (MM) model[3].
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