2018年10月23日 · PANK3 (1 μg/assay) activity at different concentrations of acetyl-CoA was determined with ATP (1 mM) in the presence (open red circles) and absence (filled circles) of 2.5 μM PZ-2891.

2024年12月25日 · PANK3 (Pantothenate Kinase 3) is a Protein Coding gene. Diseases associated with PANK3 include Immunodeficiency 31B and Neurodegeneration With Brain Iron Accumulation 1. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and coenzyme A biosynthesis.

This approach aims to alleviate defects associated with mutations in PANK2 by activating PANK3, an isoform of human PANK that is typically found in the cytosol or nucleus. A proof-of-concept preclinical study in mice showed that PZ-2891 was able to activate PANK3 by blocking an allosteric site necessary for feedback inhibition by acetyl-CoA .

2015年1月8日 · One approach to PKAN treatment would be to identify PanK1 or PanK3 activators that would stimulate CoA synthesis in tissues lacking PANK2. The PanK inhibitors would serve as tools to investigate the role of CoA in adult tissues and accelerate the identification of bypass drugs to treat PKAN disease.

2022年2月23日 · In this study, we used proton magnetic resonance spectroscopy (1 H MRS) to evaluate the brain metabolic derangements that are associated with neuronal CoA deficiency in this mouse model, with and without treatment with a newly developed Pantazine, BBP-671. 1 H MRS is particularly advantageous for this study because it permits the noninvasive exa...

Here, we report the development of a drug capable of allos-terically activating the alternate PANK isoforms as a potential PKAN therapeutic. The lead pantazine, PZ-2891, arose from the LipE-guided...

Small-molecule human PANK3 activators are a different strategy being investigated for treating PKAN. This strategy intends to activate PANK3, an isoform of human PANK ordinarily present in the cytosol or nucleus, to ameliorate abnormalities caused by mutations in PANK2.

2022年3月4日 · Accordingly, most patients with PANK2 variant are known to exhibit a specific radiologic pattern of hyperintensity within the hypointense medial globus pallidus, called the eye-of-the-tiger sign, on T2-weighted MR imaging [2].

2023年9月7日 · PANK3 is expressed ubiquitously in tissues, including the brain (Leonardi et al., 2007; Dansie et al., 2014), and the activation of this isoform provides a route to increasing cellular CoA concentrations when alternate PANK isoforms are compromised.

In this review, we will summarize this knowledge and demonstrate how it forms the backdrop to new avenues of research. Pantothenate kinase–associated neurodegeneration (PKAN) is a rare autosomal recessive disorder that largely affects children and young adults (1).