Disease relevance of W 7

• 2-aminopurine, a nonspecific protein kinase inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), a specific inhibitor of calmodulin/Ca(2+)-dependent protein kinase, and okadaic acid (OKA), a protein phosphatase inhibitor, dose-dependently inhibited Sindbis virus maturation [1].
• Inhibition of lung metastasis by a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), in mice bearing Lewis lung carcinoma [2].
• A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), proved to have antitumor activity against solid Sarcoma-180 [3].
• The antimetastatic effect of calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was examined in an experimental model of lung metastasis induced by Lewis lung carcinomas (3LL) in C57BL/6crSlc mice [2].

High impact information on W 7

• However, when 5 microM calmodulin antagonists [N-(6-aminohexyl)-1-naphthalenesulfonamide or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited [4].
• However, a well-known naphthalenesulfonamide derivative calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), could not reverse the drug resistance [5].
• N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a potent calmodulin antagonist, failed to demonstrate synergy with DDP, and activation of protein kinase C, instead of interacting antagonistically with DDP, yielded synergy [6].
• Temperature-sensitive virus-transformed normal rabbit kidney cells were sensitized to PEA by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, when these cells were grown as the transformed phenotype, whereas the nontransformed phenotype could not be sensitized [7].
• CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), but not their less-active analogues (N-(6-aminohexyl)-1-naphthalenesulfonamide; promethazine), were also found to block activation of the small GTPases Ras and Rac in stimulated neutrophils along with the extracellular signal-regulated kinases [8].

Biological context of W 7

• Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives [9].
• Calmodulin antagonists such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which bind to calmodulin (CaM) in the presence of Ca2+ and selectively inhibit CaM-induced enzyme activation, contain a hydrophobic moiety [10].
• The calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) stimulated apical endocytosis of ricin, whereas basolateral endocytosis was unaffected [11].
• Scatchard analysis revealed that N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited the binding through a significant decrease in the density of binding sites without affecting the affinity at 10 microM [12].
• N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), quin 2-AM, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and neomycin sulfate (neomycin) all potently inhibited the stimulation of lipolysis by the receptor antibody and leptin [13].

Anatomical context of W 7

• Phosphorylation of MBP in solubilized rat myelin catalyzed by the phospholipid-sensitive enzyme was inhibited by adriamycin, palmitoylcarnitine, trifluoperazine, melittin, polymyxin B, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) [14].
• In membranes prepared from area CA1, AC was stimulated by calcium in the presence of calmodulin, and the effect of calcium/calmodulin on AC in membranes was blocked by the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1- naphthalenesulfonamide (W-7) and trifluoperazine (TFP) [15].
• N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) stimulation of K+ transport in a human salivary epithelial cell line [16].
• 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 [17].
• Thrombin-stimulated secretion of endothelin-1 (ET-1) from porcine aortic endothelial cells was inhibited in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) [18].

Associations of W 7 with other chemical compounds

• The NO donor sodium nitroprusside (SNP; 10 mmol/l) and dibutyryl cGMP (100 micromol/l) accelerated epitrochlearis glucose transport four- to fivefold above basal levels (P < 0.001) in a manner similar to in vitro contractile activity and the calcium releasing agent N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7; 100 micromol/l) [19].
• The CM antagonists, pimozide, W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] and W5 [N-(6-aminohexyl)-1-napthalenesulfonamide] caused dose-dependent inhibition of hormone-stimulated Aldo production, in proportion to their reported binding affinities for CM [20].
• In addition, removal of extracellular Ca2+, depletion of the intracellular Ca2+ pool by thapsigargin, or pretreatment of PASMC with the calmodulin antagonist N-(6 aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) or with calmidazolium chloride also decreased H2O2-induced ERK1 and ERK2 activation [21].
• Although the CaM antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) and TFP, decreased and increased, respectively, the fluorescence intensity caused by 2-p-toluidinylnaphthalene-6-sulfonic acid (TNS)-CaM binding, CD-349 only slightly decreased the fluorescence of TNS bound CaM [22].
• As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 microM) as well as calmidazolium (10 nM to 1 microM) reduced the Ba2+ current [23].

Gene context of W 7

• Inhibition of calmodulin using a calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7), did not effect N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced ERK, p38 MAPK or GSK-3alpha phosphorylation, but attenuated fMLP induced PKB phosphorylation [24].
• The treatment of human uterine cervical fibroblasts with concanavalin A (ConA), or a specific calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) or trifluoperazine resulted in accumulation of an active form of matrix metalloproteinase 2 (MMP-2, gelatinase A) [25].
• In addition, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, suppressed both IL-2 production and IL-2R expression [26].
• Similarly, the calmodulin antagonist W-7 (N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide) inhibited the augmenting effect of clozapine on NMDA- and electrically evoked responses in the pyramidal cells [27].
• The cell-permeable CaM antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide), but not the CaM-dependent protein kinase II inhibitor KN93, prevents this effect [28].

Analytical, diagnostic and therapeutic context of W 7

• We have purified S-100 protein from bovine brain using Ca2+-dependent affinity chromatography on N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7)-Sepharose (Endo, T., Tanaka, T., Isobe, T., Kasai, H., Okuyama, T., and Hidaka, H. (1981) J. Biol. Chem. 256, 12485-12489) [29].

References