NSC117079 is a novel PHLPP1/2 (Pleckstrin homology domain and leucine rich repeat protein phosphatase) inhibitor that activates neuronal AKT and ameliorates staurosporine-induced cell death in neurons.

The in vitro activity of NSC117079 was evaluated in primary rat cortical neurons and astrocytes. Neurons were pretreated with NSC117079 (10–100 μM) for 35 minutes after nutrient deprivation, or co-treated with staurosporine (50–200 nM) for 24 hours; astrocytes were treated for 24 hours after seeding. NSC117079 activated AKT signaling and showed protective effects in neurons, but inhibited signaling and reduced viability in astrocytes [1].

The in vivo activity of NSC117079 was evaluated in a mouse model of osteoarthritis induced by destabilization of the medial meniscus (DMM). Twelve-week-old male C57BL/6 mice underwent right knee DMM surgery, followed by a single intra-articular injection of NSC117079 (8 mM, 3 μL; estimated intra-articular concentration ~4 mM) at 7 weeks post-surgery. The results showed that NSC117079 significantly reduced mechanical allodynia, preserved normal activity levels, and slowed articular cartilage degradation [2].