STA-013

STA-013 is a EphB tyrosine kinase inhibitor. STA-013 shows promising potency against EphB1 (IC₅₀ = 0.69 µM), EphB2 (IC₅₀ = 1.73 µM), and EphB4 (IC₅₀ = 1.02 µM) tyrosine kinases. STA-013 results a inhibition of the EphB phosphorylated signal, coupled with increased p-AKT / AKT signaling, to suggest insulin signaling activation. STA-013 inhibits EphB tyrosine kinase by enhancing insulin receptor beta ( IRβ ) signaling, and decreasing TGF-β levels in the heart. STA-013 can be used for the study of type 2 diabetes and cardiac complications (diabetic cardiomyopathy ) ^[1].

In Vivo, STA-013 (12.5, 25 and 50 mg/kg, i.p., daily for 6 weeks) promotes weight loss, improves glucose clearance and insulin sensitivity, and enhances insulin signaling in isolated brown adipose tissue and liver in high-fat diet-induced C57BL/6J mice. In these obese mice ^[1]. STA-013 (12.5, 25 and50 mg/kg, i.p., daily for 6 weeks) induces weight loss not through reduced food intake or elevated metabolic rates in DIO mice^[1].

In Vitro, STA-013 (5 µM) inhibits EphB1 (54%), EphB2 (42%), EphB4 (52%), SGK1 (47%), and PKBb (43%) without affecting the rest of 140 kinases via kinome profiling assay^[1]. STA-013 (0.032-20 µM, 96 h) significantly inhibits lipid accumulation in a dose-dependent manner in the embryonic mouse 3T3-L1 cells^[1]. STA-013 (1 µM, 30 min) results a significant reduction in basal respiration, proton leak, ATP production, and non-mitochondrial oxygen consumption, increases maximal respiration and spare respiratory capacity, exhibits a significant increase in glycolysis and glycolytic capacity and reduces palmitate oxidation in 3T3-L1 cells^[1].

References:
[1]. Tareq S,et al. Discovery of pan-EphB tyrosine kinase inhibitor for metabolic syndrome sparing EphB3 signaling in mice. Pharmacol Res. 2025 Sep;219:107900.