HPOB

A potent and selective inhibitor of HDAC6

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Background

HPOB is a highly potent and selective inhibitor of histone deacetylase 6 (HDAC6) with IC50 of 56nM, >30 fold less potent against other HDACs. [1]
HDAC6 is one of the eleven human zinc-dependent HDACs with two catalytic domains and one ubiquitin-binding domain at the C-terminal. It exhibits various biological functions including regulation of microtubule dynamics and degradation of misfolded proteins. It involves in many cellular pathways related to normal and tumor cell growth, migration and death. [1]
In normal HFS and transformed LNCaP cells, HPOB inhibited cell growth but not viability, induced acetylation of α-Tubulin, but not histones. HPOB enhanced etoposide-, doxorubicin-, and SAHA-induced cell death in transformed cell but not in normal cell. HPOB enhanced the effectives of anticancer drugs via apoptotic pathway and activated DNA damage response in transformed cell. [1]
HPOB is well-tolerated in mice carrying human prostate cancer CWR22 xenograft and enhances cytotoxicity effects of anticancer drug SAHA in these animals. [1]
参考文献:
1.? Lee JH, Mahendran A, Yao Y, Ngo L, Venta-Perez G, Choy ML, Kim N, Ham WS, Breslow R, Marks PA. Development of a histone deacetylase 6 inhibitor and its
biological effects. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15704-9.