The novel Hsp-90 inhibitor SNX7081 is significantly more potent  than 17-AAG against primary CLL cells and a range of  haematological cell lines, irrespective of lesions in the TP53  pathway.
Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP-70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.
Best
O Giles
OG
Northern Blood Research Centre, KollingInstitute, Royal North Shore Hospital, StLeonards, Sydney, NSW, Australia. gilesbest@yahoo.com
Singh
Nisha
N
Forsyth
Cecily
C
Mulligan
Stephen P
SP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016158:Genes, p53 / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; C535175:SNX-7081; C112765:tanespimycin; D051746:ZAP-70 Protein-Tyrosine Kinase