SLD1121

SLD1121 is an agonist of the Wnt/β-catenin signaling pathway that enhances Wnt signaling by targeting LRP6 ( K d: 4.52-7.49 nM). SLD1121 interacts with the intracellular domain of LRP6, stabilizes LRP6, promotes its nuclear translocation, and facilitates its binding to β-catenin, TCF4 or LEF1 in the nucleus, thereby inducing the expression of Wnt -regulated genes and stem cell-related genes. SLD1121 induces the transition of hair follicles from telogen to anagen in the mouse hair growth cycle and promotes hair growth in mice. SLD1121 is applicable to hair loss-related research ^[1].

In Vivo, SLD1121 (2%; topical; daily; 17 days) activates Wnt/β-catenin signaling in depilated C57BL/6J mice, induces hair follicle transition from telogen to anagen, and significantly enhances hair regrowth and regrown hair weight^[1].

In Vitro, SLD1121 (0-2 μM; 24 h) activates the LRP6-mediated Wnt/β-catenin signaling pathway in HEK293T cells, with an EC50 of approximately 0.21 μM^[1]. SLD1121 (1-2 μM; 24 h) activates the Wnt/β-catenin signaling pathway in HaCaT cells^[1]. SLD1121 (0.25-2 μM; 4-24 h) dose- and time-dependently increases the levels of total LRP6 protein, phosphorylated LRP6 protein, as well as ABC and β-catenin in HEK293T and HaCaT cells, without altering the mRNA expression level of LRP6^[1]. SLD1121 (2 μM; 24 h) directly interacts with LRP6 in HEK293T cells and increases the thermal stability of both endogenous and exogenous LRP6^[1]. SLD1121 (0-2 μM; 12-24 h) promotes the nuclear translocation of LRP6 and increases the nuclear β-catenin level in HaCaT cells^[1].

References:
[1]. Sun Q, et al. A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6. JACS Au. 2026;6(2):1256-1268. Published 2026 Jan 27.