Sigma-Aldrich Ezh2 Inhibitor Iii Gsk126

Assay

≥98% (HPLC)

Quality Level

100

Form

semisolid

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

brown

Solubility

DMSO: 10 mg/mL

Storage Temp.

−20°C

General Description

A cell-permeable EI1 (Cat. No. 500561) structural analog that acts as an equally potent, SAM-competitive, Ezh2/PRC2 inhibitor (K _i= 0.5 to 3 nM against wt & mutant Ezh2-containing PRC2; [SAM] = 7.5 µM) with similar selectivity over Ezh1/PRC2 (K _i= 89 nM) and other HTMases as EI1. Among panels of 14 HDACs, 11 GPCRs, and 300 kinases, only serotonin 3 receptor, JMJD2d, and CaMK1a are significantly inhibited at much higher concentrations (IC₅₀≥4 µM). Shown to inhibit the proliferation of DLBCL (IC₅₀28 nM to 5.5 µM; 6 d treatment)in vitroand completely suppress Pfeiffer (A677G) and Karpas-422 (Y641N) tumor expansion in micein vivo(50 mg/kg/d i.p.).

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.A cell-permeable EI1 (Cat. No. 500561) structural analog that acts as an equally potent, SAM-competitive, Ezh2/PRC2 inhibitor (K _i= 0.5 to 3 nM against wt, A677G, Y641F, Y641H, Y641N, Y641S, Y641C Ezh2-containing PRC2; [SAM] = 7.5 µM) with similar selectivity over Ezh1/PRC2 (K _i= 89 nM) and other HTMases as EI1. Among panels of 14 HDACs, 11 GPCRs, and 300 kinases, only serotonin 3 receptors, JMJD2d, and CaMK1a are significantly inhibited at much higher concentrations (IC₅₀= 4, 7.9, and ≥10 µM, respectively). In addition to DLBCL (diffuse large B cell lymphoma; IC₅₀ranges from 28 nM to 5.5 µM; 6 d treatment), GSK126 is also shown to inhibit the proliferation of other B-NHL (non-Hodgkin′s lymphoma) and Hodgkin′s lymphoma cell lines, being least active against MC116, HD-MY-Z, WSU-FSCCL, Toledo, NU-DUL-1, and WILL-2 (IC₅₀>10 µM; 6 d treatment). When administered at a daily i.p. dose of 50 mg/kg GSK126 is reported to completely suppress Pfeiffer (A677G) and Karpas-422 (Y641N) tumor expansion in micein vivo, while complete tumor eradication can be achieved with higher dosing regimens (150 mg/kg/day or two 300 mg/kg dosages per week).

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.Use only fresh DMSO for reconstitution.

Other Notes

McCabe, M.T., et Al. 2012.Nature. 492,108.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany