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W-7 hydrochloride

CAS No. : 61714-27-0

MCE 国际站：W-7 hydrochloride

产品活性：W-7 hydrochloride 是一种选择性的钙调蛋白 (calmodulin) 拮抗剂。W-7 hydrochloride 抑制 Ca²⁺-钙调蛋白依赖性磷酸二酯酶 (phosphodiesterase) 和肌球蛋白轻链激酶 (myosin light chain kinase)，IC₅₀ 值分别为 28 μM 和 51 μM。W-7 hydrochloride 可诱导细胞凋亡 (apoptosis)，并具有抗癌活性。

研究领域：Metabolic Enzyme/Protease  |  Cytoskeleton  |  Apoptosis  |  Membrane Transporter/Ion Channel

作用靶点：Phosphodiesterase (PDE)  |  Myosin  |  Apoptosis  |  Calmodulin

In Vitro: W-7 is distributed mainly in the cytoplasm, and inhibits proliferation of Chinese hamster ovary K1 (CHO-K1) cells. W-7 selectively blocks the phase of the cell cycle (G1/S boundary phase) in a manner. 25 μM W-7 arrests the growth of the cells at the G1/S boundary phase of the cell cycle.
W-7 (100 μM) exhibits a similar extent of antagonism between the contractile responses to carbachol and KCl. The increase in myosin light chain (P-LC) phosphate content in response to 1-min stimulation with 10 μM carbachol is inhibited by W-7. W-7 antagonizes the smooth muscle contraction through the inhibition of the initial increase in the P-LC phosphorylation.
Treatment with W-7 results in the dose-dependent inhibition of cell proliferation in various human multiple myeloma cell lines. W-7 induces G1 phase cell cycle arrest by downregulating cyclins and upregulating p21cip1. W-7 induces apoptosis via caspase activation; this occurred partly through the elevation of intracellular calcium levels and mitochondrial membrane potential depolarization and through inhibition of the STAT3 phosphorylation and subsequent downregulation of Mcl-1 protein.
W-7 competitively inhibits Ca²⁺/calmodulin-dependent phosphodiesterase with a K_i value of 300 μM.

In Vivo: W-7 (3 mg/kg; intraperitoneal injection; on 5 consecutive days per week; female BALB/c nu mice) treatment significantly reduces tumor growth in a murine MM model.

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