SLD1121(SLD-1121) is a small molecule agonist of Wnt/β-catenin signaling pathway with EC50 of 0.21 uM for LRP6-mediated Wnt activation, interacts with the intracellular domain of LRP6 (Kd=7.49 nM, LRP6-ICD domain), stabilizes LRP6, and accelerates its nuclear translocation.
SLD1121 interactes with LRP6-ICD with ITC Kd of 4.52 nM.
SLD1121 (0.125-2 uM) activates LRP6-mediated transcription in HEK293T cells.
SLD1121 (1-2 uM) upregulates the mRNA expression of Wnt target genes Axin2, LEF1, Snail1, OCT4, Twist1, Sox2, and CD44 in HaCaT cells.
SLD1121 stabilizes LRP6 through the lysosomal pathway.
SLD1121 induces the entry of LRP6 into the cell nucleus and promotes the association of LRP6 with β-catenin, promotes the association of TCF/LEF1 with the LRP6−β-catenin complex to activate the Wnt signaling pathway.
SLD1121 enhances hair regrowth in C57BL/6J mice, via the activation of Wnt/β-catenin signaling.
LRP6 is a member of the low-density lipoprotein receptor (LDLR) family, which is indispensable for Wnt signal transduction.