SLD1121

SLD1121 is an agonist of the Wnt/β-catenin signaling pathway that enhances Wnt signaling by targeting LRP6 (Kd: 4.52-7.49 nM). It interacts with the intracellular domain of LRP6, stabilizing and promoting its nuclear translocation, where it facilitates binding with β-catenin, TCF4, or LEF1, thereby inducing the expression of Wnt-regulated and stem cell-related genes. SLD1121 also stimulates the transition of hair follicles from the resting phase to the growth phase in mice, promoting hair growth, making it useful for research related to hair loss.

SLD1121, when applied at concentrations of 0-2 μM for 24 hours, activates the LRP6-mediated Wnt/β-catenin signaling pathway in HEK293T cells, with an EC50 of approximately 0.21 μM. At concentrations of 1-2 μM over 24 hours, it activates the Wnt/β-catenin signaling in HaCaT cells. Furthermore, in a dose and time-dependent manner (0.25-2 μM; 4-24 hours), SLD1121 enhances total and phosphorylated LRP6 protein levels, as well as ABC and β-catenin levels, in both HEK293T and HaCaT cells, without altering LRP6 mRNA expression. At 2 μM over 24 hours, SLD1121 interacts directly with LRP6 in HEK293T cells, increasing the thermal stability of both endogenous and exogenous LRP6. Additionally, over 12-24 hours, at 0-2 μM, SLD1121 aids in LRP6 nuclear translocation and elevates nuclear β-catenin levels in HaCaT cells.

SLD1121 (2%; topical; daily; 17 days) activates the Wnt/β-catenin signaling pathway in depilated C57BL/6J mice, initiating the transition of hair follicles from the telogen phase to the anagen phase, significantly enhancing hair regeneration and the weight of the regenerated hair.