KDAc-0001

KDAc-0001 is a novel, highly optimized, orally bioavailable small-molecule histone deacetylase 3 (HDAC3)–selective inhibitor originally developed by KDAc Therapeutics and subsequently licensed to OnKure Therapeutics as OKI-422. It belongs to the class of class I HDAC-targeting epigenetic modulators, designed to achieve potent HDAC3 inhibition with improved isoform selectivity over HDAC1/2 to widen the therapeutic window and reduce class-related toxicities. Preclinical data have shown that KDAc-0001 exhibits good CNS drug-like properties, favorable ADME/PK and toxicology profiles, and efficacy in learning and memory paradigms, fear conditioning, and rodent models of addiction, as well as anti-tumor and immunomodulatory activity in hematologic malignancy models. Mechanistically, selective HDAC3 inhibition by KDAc-0001 is intended to modulate gene expression programs involved in memory consolidation, extinction of drug-seeking or fear-related behaviors, tumor cell survival, and anti-tumor immune surveillance, supporting its development for neuropsychiatric indications such as drug addiction and fear-related disorders, and for oncology indications including diffuse large B-cell lymphoma and genetically defined solid tumors.

Other names

KDAc lead HDAC3-selective inhibitor