SGI-1027

Description: SGI-1027 is a novel and potent inhibitor of DNA methyltransferase (DNMT) with antineoplastic activity. It inhibits DNMT1, DNMT3A, and DNMT3B with IC50s of 6, 8, 7.5 uM in cell-free assays, respectively. SGI-1027 inhibits mammalian DNMTs and bacterial M. SssI in vitro. Both the endogenous and recombinant DNMTs can be inhibited by SGI-1027. The mechanism of this inhibition is that SGI-1027 competes with Ado-Met but not the substrate DNA within the cofactor binding site of the enzyme. SGI-1027 inhibits DNA methylation through directly inhibiting DNMTs. SGI-1027 reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B.

References: Cancer Res. 2009 May 15; 69(10):4277-85; Bioorg Med Chem Lett. 2013 Mar 15; 23(6):1631-5.

DNA Methyltransferase Inhibitor II; SGI1027; SGI 1027; SGI1027; N-(4-((2-amino-6-methylpyrimidin-4-yl)amino)phenyl)-4-(quinolin-4-ylamino)benzamide

InChi Key: QSYLKMKIVWJAAK-UHFFFAOYSA-N

InChi Code: InChI=1S/C27H23N7O/c1-17-16-25(34-27(28)30-17)32-20-10-12-21(13-11-20)33-26(35)18-6-8-19(9-7-18)31-24-14-15-29-23-5-3-2-4-22(23)24/h2-16H, 1H3, (H, 29, 31)(H, 33, 35)(H3, 28, 30, 32, 34)

SMILES Code: O=C(NC1=CC=C(NC2=NC(N)=NC(C)=C2)C=C1)C3=CC=C(NC4=CC=NC5=CC=CC=C45)C=C3