Discovery of potent and selective inhibitors of calmodulin-dependent kinase II (CaMKII).
Basic Information
ID: ALA4184081
Journal: Bioorg Med Chem Lett
Title: Discovery of potent and selective inhibitors of calmodulin-dependent kinase II (CaMKII).
Authors: Koltun DO, Parkhill EQ, Kalla R, Perry TD, Elzein E, Li X, Simonovich SP, Ziebenhaus C, Hansen TR, Marchand B, Hung WK, Lagpacan L, Hung M, Aoyama RG, Murray BP, Perry JK, Somoza JR, Villaseñor AG, Pagratis N, Zablocki JA.
Abstract: We hereby disclose the discovery of inhibitors of CaMKII (7h and 7i) that are highly potent in rat ventricular myocytes, selective against hERG and other off-target kinases, while possessing good CaMKII tissue isoform selectivity (cardiac γ/δ vs. neuronal α/β). In vitro and in vivo ADME/PK studies demonstrated the suitability of these CaMKII inhibitors for PO (7h rat F = 73%) and IV pharmacological studies.
CiteXplore: 29254643
DOI: 10.1016/j.bmcl.2017.10.040
Patent ID: ┄