Sm4

Sm4 is a selective and orally active SOX18 inhibitor. Sm4 inhibits SOX18-DNA binding (IC₅₀ = 97.5 μM); Sm4 disrupts the SOX18-RBPJ protein-protein interaction (IC₅₀ = 42.3 μM). Sm4 blocks SOX18 DNA binding, disrupts multiple SOX18 protein-protein interactions with RBPJ, DDX1, DDX17, ILF3, SOX7 and STAT1, modulates SOX18 chromatin binding dynamics. Sm4 exerts anti‑angiogenic and anti‑lymphangiogenic effects, reduces tumor vascular density, triggers vascular defects in zebrafish, prolongs survival in mouse metastatic cancer models. Sm4 can be used for the research of breast cancer^[1][2]. In Vitro:Sm4 (0.2 μM-3 mM) inhibits full-length mouse SOX18-DNA binding with an IC₅₀ of 97.5 μM in a FP competition assay, with no aggregation observed up to 1000 μM^[1].
Sm4 (0.3-300 μM; 1 h) selectively disrupts SOX18-RBPJ interactions with IC₅₀ values of 42.3 μM^[1].
Sm4 inhibits DNA binding of multiple SOX family HMG-box fragments with IC₅₀ values of 200-300 μM, showing a slight preference for SOX18 and SOX15^[1].
Sm4 (24 h) inhibits SOX18-dependent Vcam-1 promoter transcriptional activity in COS-7 cells with an IC₅₀ of 5.2 μM, with a CC₅₀ of 117 μM^[1].
Sm4 alters SOX18 chromatin binding dynamics in live cells, increasing the specific bound fraction and dwell time of specifically bound SOX18 in a concentration-dependent manner^[1].
Sm4 (25 μM) can selectively dysregulate SOX18-mediated transcription in human umbilical vein endothelial cells (HUVECs)^[1]. In Vivo:Sm4 (1-2 μM; exposure in culture medium) selectively inhibits SoxF transcriptional activity and arteriovenous specification in zebrafish larvae, with no effect on Sox9-mediated chondrogenesis^[1].
Sm4 (5-50 mg/kg; p.o.; daily; 10 days) dose-dependently improves survival and reduces metastasis in a mouse model of breast cancer by inhibiting tumor-induced angiogenesis and lymphangiogenesis^[1].