A01 is an inhibitor of Smad ubiquitination regulatory factor 1 (Smurf1) ubiquitin ligase (Kd = 3.67 nM).1 It inhibits Smurf1-mediated ubiquitination of Smad1/5 and increases Smad1/5 protein levels in C2C12 cells stimulated with bone morphogenic protein 2 (BMP2) in a concentration-dependent manner. A01 (2 μM) increases BMP2-induced mRNA expression of alkaline phosphatase (ALP), osteocalcin, and type-1 collagen in MC3T3-E1 mouse pre-osteoblasts.
1.Cao, Y., Wang, C., Zhang, X., et al.Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradationSci. Rep.44965(2014)