Sigma-Aldrich Ezh2 Inhibitor Ii Ei1 1pc

Assay

≥98% (HPLC)

Quality Level

100

Form

solid

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

white

Solubility

DMSO: 10 mg/mL

Storage Temp.

2-8°C

Inchi

1S/C23H26N4O2/c1-5-17(6-2)27-8-7-18-19(10-16(12-24)11-21(18)27)22(28)25-13-20-14(3)9-15(4)26-23(20)29/h7-11,17H,5-6,13H2,1-4H3,(H,25,28)(H,26,29)

Inchi Key

PFHDWRIVDDIFRP-UHFFFAOYSA-N

General Description

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_21-44and 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.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_21-44and 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 suppress cellular H3K27 dimethylation and trimethylation (1 to 10 µM) in DLBCL cultures and exhibit antiproliferation activity against DLBCL cell lines with wt or mutant Ezh2 (3.3 µM to 10 µM).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/Physiol Actions

Cell permeable: yesPrimary Target
Ezh2/PRC2Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Qi, W., et Al. 2012.Proc. Natl. Acad. Sci. USA. 109,21360.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany