TYA-018

TYA-018 is a highly selective, orally available small molecule inhibitor of histone deacetylase 6 (HDAC6), developed by Tenaya Therapeutics. It is being investigated as a disease-modifying therapy for heart failure with preserved ejection fraction (HFpEF) and dilated cardiomyopathy (DCM). TYA-018 works by inhibiting the enzymatic activity of HDAC6, which is typically upregulated in failing hearts. Mechanistically, it reverses cardiac hypertrophy and diastolic dysfunction by modulating multiple pathways: it reduces cardiac fibroblast activation (mitigating fibrosis), improves mitochondrial respiratory capacity and energetics in cardiomyocytes, and addresses systemic metabolic stress. In preclinical models, TYA-018 has demonstrated the ability to increase the acetylation of alpha-tubulin and various myofilament and calcium-regulatory proteins, thereby improving cardiac relaxation and exercise capacity. It is part of a chemical series that includes the clinical-stage candidate TN-301.