Ezh2 Inhibitor II, EI1

A cell-permeable indolocarboxamide compound that acts as a potent and selective inhibitor against Ezh2/PRC2 (Polycomb repressive complex 2; Ezh2/SUZ12/EED/AEBP2/RbAP48) HMTase activity (IC₅₀/substrate = 15 nM/H3K27me0_21-44 and 13 nM/H3K27me2_21-44, respectively, against human wt or Y641F Ezh2-containing PRC2; [SAM] = 1 µM) in a cofactor SAM-competitive manner, while inhibiting Ezh1/PRC2 only at much higher concentrations (IC₅₀ = 1.34 µM) and exhibiting no potency toward CARM 1, Dot1L, G9a, MLL, NSD3, Set7/9, SETD2, SETD8, SmyD2, or Suv39H2 (IC₅₀ >100 µM). Shown to selectively suppress cellular H3K27 dimethylation and trimethylation (1 to 10 µM in 1 to 5 days) in DLBCL (diffuse large B cell lymphoma) cultures, but not those of H3K4, H3K9, H3K36, or H3K79. EI1 is shown to exhibit antiproliferation activity against DLBCL cell lines with wt- (by 90% in G401 with 3.3 µM EI1; by 78% in Toledo with 10 µM EI1; 14 d incubation) or mutant- Ezh2 (by &gt96% in WSU-DLCL2/Y641F, SU-DHL6/Y641N, Karpas422/Y641N, and DB/Y641N cultures with 3.3 µM EI1; by &gt96% in SU-DHL4 cultures with10 µM EI1; 14 d incubation), while being less effective against MEF (by 40% in 11 days at 3.3 µM) and ineffective toward wt Ezh2-expressing GA10 and OCI-LY19.

Cell permeable: yes

Primary Target
Ezh2/PRC2

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Qi, W., et al. 2012. Proc. Natl. Acad. Sci. USA.109, 21360.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)