W-7 

W-7 is a selective calmodulin antagonist. W-7 inhibits the Ca²⁺-calmodulin-dependent phosphodiesterase and myosin light chain kinase with IC₅₀ values of 28 μM and 51 μM, respectively. W-7 induces apoptosis and has antitumor and vascular relaxing activity. W-7 is a blocker of Kv4.3 and can be used for research of arrhythmias^{[1][2][3][4][5][6]}.

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^[1].
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^[2].
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^[3].
W-7 competitively inhibits Ca²⁺/calmodulin-dependent phosphodiesterase with a K_i value of 300 μM^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

340.87

C₁₆H₂₁ClN₂O₂S

65595-90-6

Solid

Light yellow to yellow

O=S(C1=C2C=CC=C(Cl)C2=CC=C1)(NCCCCCCN)=O

Room temperature in continental US; may vary elsewhere.

• [1]. H Hidaka, et al. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a Calmodulin Antagonist, Inhibits Cell Proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354-7.  [Content Brief]

  [2]. M Asano. Divergent Pharmacological Effects of Three Calmodulin Antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), Chlorpromazine and Calmidazolium, on Isometric Tension Development and Myosin Light Chain Phosphorylation in Intact Bovine Tracheal Smooth Muscle. J Pharmacol Exp Ther. 1989 Nov;251(2):764-73.  [Content Brief]

  [3]. H Itoh, et al. Direct Interaction of Calmodulin Antagonists With Ca2+/calmodulin-dependent Cyclic Nucleotide Phosphodiesterase. J Biochem. 1984 Dec;96(6):1721-6.H Itoh, et al. Direct Interaction of Calmodulin Antagonists With Ca2+/calmodulin-dependent Cyclic Nucleotide Phosphodiesterase. J Biochem. 1984 Dec;96(6):1721-6.  [Content Brief]

  [4]. Shigeyuki Yokokura, et al. Calmodulin Antagonists Induce Cell Cycle Arrest and Apoptosis in Vitro and Inhibit Tumor Growth in Vivo in Human Multiple Myeloma. BMC Cancer. 2014 Nov 26;14:882.  [Content Brief]

  [5]. Qu YJ, et al. W-7 modulates Kv4.3: pore block and Ca2+-calmodulin inhibition. Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2364-77.  [Content Brief]

  [6]. Gbadebo TD, et al. Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that predicts initiation of torsade de pointes. Circulation. 2002 Feb 12;105(6):770-4.  [Content Brief]