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 hydrochloride 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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