W-7 hydrochloride

Names

[ Name ]:
W-7 hydrochloride

[Synonym ]:
W-7
n-(6-aminohexyl)-5-chloronaphthalene-1-sulfonamide hydrochloride
1-Naphthalenesulfonamide, N-(6-aminohexyl)-5-chloro-, hydrochloride (1:1)
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide,HCl
W-7 HYDROCHLORIDE
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (1:1)
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide monohydrochloride
MFCD00012559
L66J BSWM6Z GG &&HCl
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride
N-(6-aminohexyl)-1-naphthalene sulfonamide hydrochloride
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, hydrochloride (1:1)
N-(6-Aminohexyl)-5-chloronaphthalene-1-sulfonamide hydrochloride (1:1)

Biological Activity

[Description]:

W-7 hydrochloride is a selective calmodulin antagonist. W-7 hydrochloride inhibits the Ca2+-calmodulin-dependent phosphodiesterase and myosin light chain kinase with IC50 values of 28 μM and 51 µM, respectively[1][2]. W-7 hydrochloride induces apoptosis and has antitumor activity[3].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Neuronal Signaling >> CaMK

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

Signaling Pathways >> Cytoskeleton >> Myosin

[Target]

IC50: 28 μM (Phosphodiesterase) and 51 µM (Myosin light chain kinase)[1]

[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[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 Ki value of 300 μM[4].

[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[3]. Animal Model: Female BALB/c nu mice (6-week-old) injected with RPMI 8226 cells[3] Dosage: 3 mg/kg Administration: Intraperitoneal injection; on 5 consecutive days per week Result: Significantly reduced tumor growth in a murine MM model.

[References]

[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.

[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.

[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.

[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.

Chemical & Physical Properties

[ Boiling Point ]:
518.8ºC at 760 mmHg

[ Melting Point ]:
220-222 °C

[ Molecular Formula ]:
C₁₆H₂₂Cl₂N₂O₂S

[ Molecular Weight ]:
377.329

[ Flash Point ]:
267.6ºC

[ Exact Mass ]:
376.077911

[ PSA ]:
80.57000

[ LogP ]:
6.26460

[ Storage condition ]:
−20°C

[ Water Solubility ]:
methanol: 25 mg/mL, clear, colorless

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xi

[ Safety Phrases ]:
S22-S24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
QK0786000

Articles

Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.

Nat. Chem. Biol. 5 , 765-71, (2009)

Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened...

Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma.

BMC Cancer 14 , 882, (2014)

Human multiple myeloma (MM) is an incurable hematological malignancy for which novel therapeutic agents are needed. Calmodulin (CaM) antagonists have been reported to induce apoptosis and inhibit tumo...

Calmodulin and PI(3,4,5)P₃ cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production.

Sci. Signal. 7(337) , ra74, (2014)

Precise regulation of the kinetics and magnitude of Ca(2+) signaling enables this signal to mediate diverse responses, such as cell migration, differentiation, vesicular trafficking, and cell death. W...