Synthesis and evaluation of geldanamycin-testosterone hybrids.
Geldanamycin (GDM) binds to the Hsp90 chaperone protein resulting in the degradation of several important signaling proteins. A series of GDM-testosterone linked hybrids has been synthesized and evaluated for activity against prostate cancer cell lines. The hybrid with the greatest activity exhibits potent and selective cytotoxicity against prostate cancer cells containing the androgen receptor.
Kuduk
S D
SD
Departement of Medicine, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
Harris
T C
TC
Zheng
F F
FF
Sepp-Lorenzino
L
L
Ouerfelli
Q
Q
Rosen
N
N
Danishefsky
S J
SJ
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016227:Benzoquinones; D004341:Drug Evaluation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047029:Lactams, Macrocyclic; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011809:Quinones / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D011960:Receptors, Estrogen; D013739:Testosterone; C001277:geldanamycin