HPOB

HPOB is a highly potent and selective inhibitor of HDAC6 with an IC₅₀ of 56 nM. HPOB displays >30 fold less potent against other HDACs. HPOB enhances the effectiveness of DNA-damaging anticancer agents in transformed cells but not normal cells. HPOB does not block the ubiquitin-binding activity of HDAC6^[1]. In Vitro: HPOB (8, 16, or 32 μM; 72 hours) inhibits growth, however, not viability, of normal or transformed cells^[1].
In normal (HFS) and transformed (LNCAP, U87, and A549) cells, HPOB causes accumulation of acetylated α-tubulin and acetylated peroxiredoxin, substrates of HDAC6, but not of acetylated histones. HPOB enhances etoposide-, doxorubicin-, and SAHA-induced transformed cell ((LNCAP, U87, and A549 cells) death but not normal cell death^[1].
In LNCaP cells cultured with HPOB and etoposide, there was an increase in cleaved PARP, a marker of apoptosis. Combination of HPOB with etoposide increased the accumulation of DNA damage compared with etoposide alone as evidenced by accumulation of γH2AX in LNCaP cells^[1].
HPOB attenuates corticosterone-induced injury in rat adrenal pheochromocytoma PC12 cells by inhibiting mitochondrial GR translocation and the intrinsic apoptosis pathway^[2]. In Vivo: HPOB (300 mg/kg; i.p.; daily for 18 days) and SAHA (50 mg/kg) causes suppression of the growth of established CWR22 tumors^[1].