Biological Activity
Potent inhibitor of cdk4/cyclin D1 (IC 50 = 59 nM). Also active against CaM kinase II (IC 50 = 25 nM) but displays selectivity over several other kinases in vitro (IC 50 values for inhibition of PKA and PKC are > 2 and > 100 μ M respectively). Inhibits human cytomegalovirus (HCMV) replication in vitro (IC 50 = 200 nM).
in vitro
arcyriaflavin a is a potent, selective inhibitor of hcmv replication in cell culture, and the anti-hcmv activity appeared no relation to the inhibition of protein kinase c. the imide nh was identified to be essential for anti-hcmv activity [1]. arcyriaflavin a also has been showed the inhibitory activity against d1/cdk4 with a ic50 of 59 nm. based on x-ray co-crystal structure of staurosporine and the human cdk2, the acidic proton of the maleimide moiety and the carbonyl group play critical roles by acting as a hydrogen bond donor and acceptor in the atp binding pocket of cdk2 [2].
References
[1] slater mj, cockerill s, baxter r, bonser rw, gohil k, gowrie c, robinson je, littler e, parry n, randall r, snowden w. indolocarbazoles: potent, selective inhibitors of human cytomegalovirus replication. bioorg med chem. 1999 jun;7(6):1067-74.
[2] zhu g, conner s, zhou x, shih c, brooks hb, considine e, dempsey ja, ogg c, patel b, schultz rm, spencer cd, teicher b, watkins sa. synthesis of quinolinyl/isoquinolinyl[a]pyrrolo [3,4-c] carbazoles as cyclin d1/cdk4 inhibitors. bioorg med chem lett. 2003 apr 7;13(7):1231-5.
