Synthesis and evaluation of geldanamycin-estradiol hybrids.
Geldanamycin (GDM) binds to the Hsp90 chaperone protein and causes the degradation of several important signalling proteins. A series of novel estradiol-geldanamycin hybrids has been synthesized and evaluated for their ability to induce the selective degradation of the estrogen receptor (ER). The hybrid compounds are active and more selective than the parent causing degradation of ER and HER2, but not other GDM targets.
Kuduk
S D
SD
Department of Medicine, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
Zheng
F F
FF
Sepp-Lorenzino
L
L
Rosen
N
N
Danishefsky
S J
SJ
D016227:Benzoquinones; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D004958:Estradiol / Q000138:chemical synthesis*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D047029:Lactams, Macrocyclic; D008956:Models, Chemical; D011809:Quinones / Q000138:chemical synthesis*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D011960:Receptors, Estrogen; D004958:Estradiol; C001277:geldanamycin