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• W2034702455 abstract "Our objective is to describe the basic chemical and biological properties of the new calmodulin antagonist HMN-709 (2-[N-(2-aminoethyl)-N-(4-chlorobenzenesulfonyl)]amino-N-(4-flu orocinnamyl)-N-methylbenzylamine). This newly synthesized compound was found to inhibit the Ca2+/calmodulin-dependent activation of calmodulin kinase I, smooth muscle myosin light chain kinase and Ca2+-phosphodiesterase with IC50 values of 1.57+/-0.21, 2.29+/-0.09 and 0.30+/-0.08 microM (mean+/-S.E.), respectively. This compound showed little or no effect on the Ca2+/calmodulin-independent activation of protein kinase A, protein kinase C and basal phosphodiesterase. In addition, HMN-709 inhibited calmodulin kinase I competitively with respect to calmodulin (Ki=0.88 microM) and non-competitively with respect to ATP. Affinity chromatography, with HMN-709-coupled Sepharose HP, showed that the compound bound to calmodulin in a Ca(2+)-dependent manner and did not bind to calmodulin kinase I. These results suggest that HMN-709 antagonizes calmodulin by binding to Ca2+/calmodulin. HMN-709 inhibited collagen-induced platelet aggregation with an IC50 value of 11.80+/-0.86 microM (mean+/-S.E.) without inhibiting phorbol 12,13-dibutyrate-induced aggregation at doses up to 12 microM. HMN-709 appears to be a new, membrane-permeable calmodulin antagonist that may be used for studying the involvement of calmodulin in cellular processes." @default.
• W2034702455 created "2016-06-24" @default.
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• W2034702455 date "1996-01-01" @default.
• W2034702455 modified "2023-09-23" @default.
• W2034702455 title "HMN-709, a Chlorobenzenesulfonamide Derivative, Is a New Membrane-Permeable Calmodulin Antagonist" @default.
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• W2034702455 doi "https://doi.org/10.1254/jjp.72.127" @default.
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