SGI-1027 has been used as a DNA methyltransferase inhibitor to study its effects on gene expression during osteogenic differentiation. It has also been used as a DNA methyltransferase 3a inhibitor to study its effects on interleukin-6 (IL-6)-induced loss of forkhead box P3 (Foxp3) gene expression in B-lymphocyte-induced maturation protein 1 (Blimp1)-Treg cells.
Biochem/physiol Actions
SGI-1027 is a DNA methyltransferase (DNMT) inhibitor with IC50 values of 6-13 µM for DNMT3B, DNMT3A and DNMT1. SGI-1027 directly inhibits DNMT activity by competing with the cofactor, S-adenosylmethionine (SAM) in the methylation reaction. SGI-1027 treatment of cancer cell lines induced degradation of DNMT1, but not DNMT3A or DNMT3B, and in RKO cells caused re-expression of the silenced tumor supressor genes p16, MLH1 and TIMP3.