Background:

IC50: 0.2 μM for HCMV [1], 0.14 μM for D1–CDK4 [2]

The natural product Arcyriaflavin A, unsubstituted indolocarbazole, was a potent selective inhibitor of human cytomegalovirus (HCMV) replication. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised.

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].

In vivo: So far, no in vivo study has been conducted.

Clinical trial: So far, no clinical study has been conducted.

参考文献:
[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.