NSC117079 is an inhibitor of PHLPP.

PHLPP inhibitors (NSC117079 and NSC45586;?benzoic acid, 5-[2-[4-[2-(2,4-diamino-5-methylphenyl)diazenyl]phenyl]diazenyl]-2-hydroxy-,sodium salt.) in rat cortical neurons and astrocytes and compared the biochemical response of these agents with short hairpin RNA (shRNA)-mediated PHLPP1 knockdown (KD).?In neurons, both PHLPP1 KD and experimental PHLPP inhibitors activated AKT and ameliorated staurosporine (STS)-induced cell death.?Unexpectedly, in astrocytes, both inhibitors blocked AKT activation, and NSC117079 reduced viability.?Only PHLPP2 KD mimicked PHLPP inhibitors on astrocyte biochemistry.?This suggests that these inhibitors could have possible detrimental effects on astrocytes by blocking novel PHLPP2-mediated prosurvival signaling mechanisms.

Animals treated with the Phlpp inhibitor seven weeks after injury maintain normal activity levels, while those in the control group travel shorter distances and are less active three months after the joint injury.?NSC117079 also increases production of cartilage extracellular matrix components (glycosaminoglycans and aggrecan) in over 90% of human articular cartilage explants from osteoarthritis patients and increased phosphorylation of Phlpp1 substrates (AKT2, ERK1/2 and PKC) in human articular chondrocytes.A single intraarticular injection of the Phlpp inhibitor NSC117079 attenuates mechanical allodynia and slows articular cartilage degradation in joints with a destabilized meniscus[1].