Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport
Data(s) |
01/06/2013
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Resumo |
2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/44484/1/BioorgMedChem2013.pdf Hofer, Alexandre; Kovacs, Gergely; Zappatini, Anna; Leuenberger, Michele; Hediger, Matthias A.; Lochner, Martin (2013). Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport. Bioorganic & medicinal chemistry, 21(11), pp. 3202-3213. Elsevier 10.1016/j.bmc.2013.03.037 <http://dx.doi.org/10.1016/j.bmc.2013.03.037> doi:10.7892/boris.44484 info:doi:10.1016/j.bmc.2013.03.037 info:pmid:23602525 urn:issn:0968-0896 |
Idioma(s) |
eng |
Publicador |
Elsevier |
Relação |
http://boris.unibe.ch/44484/ http://www.sciencedirect.com/science/article/pii/S0968089613002538 |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Hofer, Alexandre; Kovacs, Gergely; Zappatini, Anna; Leuenberger, Michele; Hediger, Matthias A.; Lochner, Martin (2013). Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport. Bioorganic & medicinal chemistry, 21(11), pp. 3202-3213. Elsevier 10.1016/j.bmc.2013.03.037 <http://dx.doi.org/10.1016/j.bmc.2013.03.037> |
Palavras-Chave | #570 Life sciences; biology #610 Medicine & health #540 Chemistry |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |