19308-92-0Relevant academic research and scientific papers
Structure-activity relationship of cantharidin derivatives to protein phosphatases 1, 2A1, and 2B
Sodeoka, Mikiko,Baba, Yoshiyasu,Kobayashi, Satoko,Hirukawa, Nozomu
, p. 1833 - 1836 (1997)
The effects of structural modification of cantharidin on the inhibition of protein Ser/Thr phosphatases are described. Removal of the methyl substituents at C2 and C3 in cantharidin improved the inhibition of PP2B. In contrast, introduction of a substituent to C1/C4-position drastically decreased inhibition of PP1 and PP2A1. PP2B was found to be quite tolerant to modifications at the C5 position.
7-Oxanorbornane and norbornane mimics of a distorted β-D- mannopyranoside: Synthesis and evaluation as β-mannosidase inhibitors
Buser, Stephan,Vasella, Andrea
, p. 3151 - 3173 (2007/10/03)
The racemic 7-oxanorbornanyl and norbornanyl aminoalcohols 3, 4, 42, 45, and 46 were synthesized and tested as snail β-mannosidase inhibitors. The amino tetraol 3 was obtained from the known sulfonyl acrylate 9 and furan 10. Esterification provided 11 tha
Structure-based design of a highly selective catalytic site-directed inhibitor of Ser/Thr protein phosphatase 2B (calcineurin)
Baba, Yoshiyasu,Hirukawa, Nozomu,Tanohira, Naoto,Sodeoka, Mikiko
, p. 9740 - 9749 (2007/10/03)
Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transductions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1,5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.
