4jib
Crystal structure of of PDE2-inhibitor complexCrystal structure of of PDE2-inhibitor complex
Structural highlights
Publication Abstract from PubMedWe identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition. Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors.,Plummer MS, Cornicelli J, Roark H, Skalitzky DJ, Stankovic CJ, Bove S, Pandit J, Goodman A, Hicks J, Shahripour A, Beidler D, Lu XK, Sanchez B, Whitehead C, Sarver R, Braden T, Gowan R, Shen XQ, Welch K, Ogden A, Sadagopan N, Baum H, Miller H, Banotai C, Spessard C, Lightle S Bioorg Med Chem Lett. 2013 Mar 28. pii: S0960-894X(13)00400-9. doi:, 10.1016/j.bmcl.2013.03.072. PMID:23582272[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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