SKLB06329 is a potent and selective inhibitor of type I PRMTs. It demonstrates strong selectivity for PRMT6 (IC50= 3.86 nM) without significantly inhibiting type II/III PRMTs (such as PRMT5/7) or various protein lysine methyltransferases [PKMTs]. SKLB06329 effectively suppresses the proliferation of triple-negative breast cancer [TNBC] cells, induces apoptosis, and inhibits the expression of asymmetric dimethylarginine [ADMA] within cells. This compound is applicable for research related to triple-negative breast cancer.

PRMT6:3.86 nM

SKLB06329 (compound B9) effectively inhibits the proliferation of TNBC cells, with IC50 values of 29.94 μM for MDA-MB-231 cells and 3.93 μM for Hs578T cells, comparable to the positive control MS023. It forms hydrogen bonds with several amino acids in PRMT1, including Glu65, Met164, and Tyr170, resulting in potent inhibition of type I PRMTs activity. At concentrations of 5-40 μM, SKLB06329 significantly reduces colony formation in MDA-MB-231 and Hs578T cells, even decreasing colony numbers and cellular density at the lowest concentration of 5 μM. It induces apoptosis effectively at concentrations of 10-80 μM over six days and inhibits ADMA expression in TNBC cells (MDA-MB-231 and Hs578T) in a concentration-dependent manner, indicating intracellular inhibition of type I PRMTs methylation function. Additionally, SKLB06329 (0-80 μM over six days) demonstrates a PRMT1-dependent antiproliferative effect in MDA-MB-231 cells.