Compound 30666 is a specific small molecule inhibitor of IgH enhancer transcriptional activity with IC50 of 2.1 uM, inhibits immunoglobulin production by MM cells.
Compound 30666 does not act on other enhancer/promoter driven systems.
Compound 30666 (5 uM) represses the expression of IgH translocation-induced oncogenes (CCND1, FGFR3/MMSET, and MYC) in MM and NHL cell lines.
Compound 30666 exhibits selective cytotoxicity in cells positive for IgH translocations with mean EC50 of 4.0 uM, while less sensitive to IgH translocation negative cells and normal cells (EC50=51 uM).
Compound 30666 (5 mg/kg, i.p.) exhibits favorable pharmacokinetic properties and anti-MM activity in vivo.
Compound 30666 downregulates MYC levels in BL cell lines and alters IGH enhancer RNA expression, cuases a global decrease of H3K27ac and an increase of H3K4me1.
Compound 30666 exhibits consistent growth inhibition in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL).