PZ-2891

PZ-2891 (also known as Pantazine 2891) is an orally bioavailable and brain-penetrant small molecule modulator of the pantothenate kinase (PANK) family of enzymes, specifically targeting PANK1β, PANK2, and PANK3. Developed by St. Jude Children's Research Hospital, the compound is being investigated for the treatment of pantothenate kinase-associated neurodegeneration (PKAN), a rare and debilitating neurodegenerative disorder caused by mutations in the PANK2 gene that lead to a deficiency in coenzyme A (CoA). PZ-2891 exhibits a unique concentration-dependent mechanism of action, functioning as an allosteric activator at lower concentrations and an orthosteric inhibitor at higher concentrations. In preclinical mouse models, PZ-2891 has demonstrated the ability to cross the blood-brain barrier, increase CoA levels in the brain and liver, ameliorate locomotor impairments, and extend lifespan, suggesting significant therapeutic potential for restoring metabolic homeostasis in PKAN patients.

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CAS 2170608-82-7CAS2170608-82-7CAS-2170608-82-7