PNU-177864 is primarily used in scientific research as a selective inhibitor of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme plays a key role in regulating cortisol levels within tissues, particularly in the liver, adipose tissue, and brain. By inhibiting 11β-HSD1, PNU-177864 helps reduce local cortisol production, making it a valuable tool in studying metabolic disorders such as type 2 diabetes, obesity, and metabolic syndrome.

It has been used in preclinical models to investigate the effects of reduced intracellular cortisol on insulin sensitivity, glucose metabolism, and lipid profiles. Results from these studies suggest that inhibition of 11β-HSD1 can improve insulin resistance and lower blood glucose levels without affecting systemic cortisol concentrations, highlighting its potential as a therapeutic target.

Additionally, PNU-177864 has been employed in neuroscience research to explore the role of local cortisol regeneration in cognitive function and stress-related disorders. Due to its selectivity and potency, it serves as a reference compound in the development of new inhibitors aimed at treating conditions associated with glucocorticoid excess in specific tissues.