Nodakenetin

Nodakenetin is an orally active Wnt/β-catenin pathway activator. Nodakenetin reduces the level of DKK1, and upregulates c-Myc, cyclin D1 and survivin. Nodakenetin induces osteoprogenitor cell differentiation, upregulates bone formation biomarkers and prevents bone microstructure degeneration. Nodakenetin induces irritant skin reactions. Nodakenetin improves bone microstructure and histomorphometric parameters in osteoporotic mouse models. Nodakenetin can be used for osteoporosis-related research^[1][2][3]. In Vitro:Nodakenetin (0-100 μM; 24-72 h) selectively activates β-catenin/TCF-responsive transcriptional activity in HEK293 cells in a concentration-dependent manner (up to 50 μM) in vitro, and does not induce cytotoxicity at concentrations up to 100 μM^[1].
Nodakenetin (0-100 μM; 24 h) activates the Wnt/β-catenin pathway in HEK293 cells by downregulating DKK1 and β-catenin degradation, regulating GSK3β phosphorylation, and upregulating the downstream target proteins c-Myc, cyclin D1 and survivin in a concentration-dependent manner^[1].
Nodakenetin (0-100 μM; 12-72 h) activates the Wnt/β-catenin pathway in MC3T3-E1 preosteoblasts by downregulating DKK1 and β-catenin degradation, upregulating downstream target proteins, and increasing β-catenin mRNA levels in a concentration-dependent manner; it shows no cytotoxicity at concentrations up to 100 μM^[1].
Nodakenetin (25-100 μM; 6-10 days) promotes osteoblastic differentiation and maturation of MC3T3-E1 cells by increasing extracellular matrix mineralization levels and alkaline phosphatase (ALP) activity in both differentiated and undifferentiated cells in a concentration-dependent manner^[1].
Nodakenetin (0-100 μM; 12-24 h) upregulates the expression of BMP2, BMP4 and Runx2 at both protein and mRNA levels in a concentration-dependent manner, and induces osteoblastic differentiation of MC3T3-E1 cells^[1].
Nodakenetin (Compound 6) (2.5-200 mg/mL; 24 h) exhibits low cytotoxicity against Artemia salina nauplii, with an LC₅₀ of 249.289 mg/mL after 24 h of incubation^[2].
Nodakenetin (125 μg/mL; 18 h) weakly inhibits LPS (HY-D1056)-induced NO production in RAW 264.7 macrophages, with an inhibition rate of 20.72% at the concentration of 125 μg/mL^[3]. In Vivo:Nodakenetin (50-100 mg/kg; p.o.; daily; 12 weeks) dose-dependently improves bone microstructure and histomorphometric parameters in ovariectomized (OVX)-induced osteoporotic mice^[1].
Nodakenetin (0.0078125-1 μg/μL; topical administration on mouse ear; single administration) exhibits weak and persistent irritation on the ear of albino mice^[2].