SKL2001 (Synonyms: Wnt Agonist II)

SKL2001 is an agonist of the Wnt/β-catenin pathway. SKL2001 stabilizes intracellular β-catenin via disruption of the Axin/β-catenin interaction, and can be applied to regulate mesenchymal stem cell differentiation^[1].

SKL2001 (5, 10, and 30μM; 3d) consistently induced the accumulation of intracellular β-catenin and inhibited the expression of C/EBPα and PPARγ. The exposure of 3T3-L1 and ST2 cells to SKL2001 resulted in a concentration-dependent decrease in lipid droplet accumulation in response to insulin^[1]. SKL2001 (10, 30μM; 15h) upregulated β-catenin responsive transcription by increasing the intracellular β-catenin protein level and inhibited the phosphorylation of β-catenin at residues Ser33/37/Thr41 and Ser45^[1].Treatment of ECs with SKL2001 at 30μM for 12h induced the expressions of MALAT1, ZO-1 and Occludin^[2].

SKL2001 (6mg/kg; ip; 7d) treatment results in a decrease in the permeability of the aortic wall of the mice^[2].In the doxorubicin mouse model, SKL2001 (4mg/kg; ip; 7d) stimulated rCFs to activate the Wnt/β-catenin pathway, inducing cardiac dysfunction and myocardial fibrosis in mice^[3].

References:
[1]. Gwak J, Hwang S G, Park H S, et al. Small molecule-based disruption of the Axin/β-catenin protein complex regulates mesenchymal stem cell differentiation[J]. Cell research, 2012, 22(1): 237-247.
[2]. Yang F, Zhang Y, Zhu J, et al. Laminar flow protects vascular endothelial tight junctions and barrier function via maintaining the expression of long non-coding RNA MALAT1[J]. Frontiers in Bioengineering and Biotechnology, 2020, 8: 647.
[3]. Yuan M, Shi H, Wang B, et al. Targeting SOCS2 alleviates myocardial fibrosis by reducing nuclear translocation of β-catenin[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2024, 1871(7): 119804.