Histone deacetylases (HDACs) play a critical role in epigenomic regulation of cancer cell signaling. HDAC inhibitors to-date have faced challenges due to poor isoform selectivity and narrow therapeutic indices. In this first disclosure, Diamond and colleagues report the discovery and preclinical development of the novel, orally bioavailable, class I-targeting HDAC inhibitor, OKI-179 (NCT03931681). OKI-179 was active against solid tumors in preclinical cancer models with a favorable pharmacokinetic profile and on-target pharmacodynamic effects. OKI-179 is a promising next generation HDAC inhibitor suitable for combining with other targeted agents based on its potency, desirable class I HDAC inhibition profile and oral bioavailability.

Most men on androgen deprivation therapy (ADT) with advanced hormone-sensitive prostate cancer (HSPC) will develop castration resistant prostate cancer (CRPC), a lethal form of prostate cancer (PC). Previously, our group has demonstrated that IKKε is overexpressed in CRPC and its expression is directly correlated with aggressive PC in patients. In...

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