17-allylamino-17-(demethoxy)geldanamycin (17-AAG) is a potent and effective inhibitor of human cytomegalovirus replication in primary fibroblast cells.
The 90 % human cytomegalovirus inhibitory concentration of 17-allylamino-17-(demethoxy)geldanamycin (17-AAG) was 0.1 nM and 50 % cytotoxicity required at least a 10 μM concentration. Three molecular targets may explain the antiviral activities of this compound. These are (1) heat shock protein maturation complexes, (2) host cell cycle progression and (3) phosphatidylinositol 3-kinase signaling. However, the data suggested a mechanism of action where 17-AAG blocked immediate-early protein transactivation.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. eversdl@comcast.net
David L
DL
Evers
Chih-Fang
CF
Chao
Zhigang
Z
Zhang
Eng-Shang
ES
Huang
D016227:Benzoquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D016227:Benzoquinones; D017874:Immediate-Early Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin