tanespimycin
Overview
Tanespimycin (17-AAG) is a geldanamycin-derived HSP90 inhibitor. NQO1 bioactivates 17-AAG to the more potent form 17-DMAG (alvespimycin). GI50 for tanespimycin is inversely correlated with NQO1 expression in hepatocellular carcinoma cell lines. Tumors with KEAP1 or NFE2L2 mutations have elevated NQO1 and may be selectively sensitive, except in carriers of the NQO1 P187S (NQO1*2) loss-of-function polymorphism.
Evidence in the corpus
- HSP90 inhibitors tanespimycin (17-AAG) and alvespimycin (17-DMAG) nominated as candidate strategies for KEAP1/NFE2L2-mutated HCC: GI50 for 17-AAG/17-DMAG was inversely correlated with NQO1 expression (Pearson r = −0.56, P = 0.0015) across 29 liver cancer cell lines; two of three KEAP1-mutant lines were highly sensitive; the third (MHCC97H) was resistant due to homozygous NQO1 P187S (rs1800566) variant that destabilizes NQO1 protein PMID:25822088
Resistance mechanisms
- NQO1 P187S (rs1800566) polymorphism destabilizes NQO1 protein and confers resistance to tanespimycin/alvespimycin in KEAP1-mutated HCC cell line MHCC97H PMID:25822088
Cancer types (linked)
Sources
This page was processed by crosslinker on 2026-05-14.