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Development of a Histone Deacetylase 6 Inhibitor and Its Biological Effects

Development of a Histone Deacetylase 6 Inhibitor and Its Biological Effects

Ju-Hee Lee, Adaickapillai Mahendran, Yuanshan Yao, Lang Ngo, Gisela Venta-Perez, Megan L Choy, Nathaniel Kim, Won-Seok Ham, Ronald Breslow, Paul A Marks

Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15704-9.

PMID: 24023063

Abstract:

Development of isoform-selective histone deacetylase (HDAC) inhibitors is important in elucidating the function of individual HDAC enzymes and their potential as therapeutic agents. Among the eleven zinc-dependent HDACs in humans, HDAC6 is structurally and functionally unique. Here, we show that a hydroxamic acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB) selectively inhibits HDAC6 catalytic activity in vivo and in vitro. HPOB causes growth inhibition of normal and transformed cells but does not induce cell death. HPOB enhances the effectiveness of DNA-damaging anticancer drugs in transformed cells but not normal cells. HPOB does not block the ubiquitin-binding activity of HDAC6. The HDAC6-selective inhibitor HPOB has therapeutic potential in combination therapy to enhance the potency of anticancer drugs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1429651502	HPOB		1429651-50-2	Price

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