KY-02327, a metabolically stabilized analog of KY-02061, serves as a potent inhibitor of the Dishevelled (Dvl)-CXXC5 interaction. This compound activates the Wnt/β-catenin pathway, thereby promoting osteoblast differentiation.

KY-02327 treatment (1-10 μM; 2 days) on MC3T3E1 cells, a murine pre-osteoblast cell line, enhances β-catenin protein level and Runx2, as well as nuclear β-catenin accumulation, in a dose-dependent manner [1]. Additionally, KY-02327 (1-10 μM) elevates the mRNA expression of osteoblast differentiation markers, collagen 1a (Col1a) and osteocalcin (OCN) [1].

KY-02327 (20 mg/kg; p.o.; administered for 5 consecutive days each week for 4 weeks) effectively mitigates bone loss in an ovariectomized (OVX) mouse model, demonstrating its potential for osteoporosis treatment by stimulating bone growth[1]. In this study, 8-week-old female BL6 mice were treated following the specified regimen, resulting in increased bone formation in the femur, confirmed by calcein labeling, compared to vehicle-treated OVX mice.