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Data Sheet
Product Name:Cat. No.:CAS No.:
Molecular Formula:Molecular Weight:Target:Pathway:Solubility:
A–366HY-125831527503-11-2C19H27N3O2329.44
Histone MethyltransferaseEpigenetics10 mM in DMSO
BIOLOGICAL ACTIVITY:
A–366 is a peptide–competitive inhibitor of G9a/GLP with an enzymatic IC50 of ~3 nM and >100–fold selectivity over othermethyltransferases and other non–epigenetic targets.IC50 value: 3 nMTarget: HMTase
in vitro: A–366 is a cell–active G9a/GLP small molecule inhibitor. The potency and selectivity of A–366 made it an ideal candidate toprobe the cellular activities of G9a/GLP. A–366 reduced the total levels of H3K9me2 in a time and concentration dependent mannerwith a cellular EC50 of ~300 nM. A–366 has significantly less cytotoxic effects on the growth of tumor cell lines compared to otherknown G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2. Additionally, the selectivityprofile of A–366 has aided in the discovery of a potentially important role for G9a/GLP in maintenance of leukemia. Long termtreatment of leukemia cell lines with A–366 results in differentiation and inhibition of growth
in vivo: Mice treated with A–366 administered via osmotic mini–pump at 30 mg/kg/day for two weeks showed no overt toxicity.Furthermore, treatment of a flank xenograft leukemia model with A–366 resulted in growth inhibition consistent with the profile ofH3K9me2 reduction observed.
PROTOCOL (Extracted from published papers and Only for reference)
Cell assay (flow cytometry) [1]
MV4;11 or HL–60 cells were incubated with the indicated concentrations of A–366 for the indicated number of days. Cells werecollected and then washed with cold PBS before staining with 0.5ml PBS containing 50 μg/ml propidium iodide (PI), 0.1mg/ml RNaseA, 0.1% BSA, and 0.1% Triton–X100 for 20 minutes. Cell cycle distribution was analyzed using a BD LSR–II flow cytometer.Animal administration [1]
Tumor cells were mixed with 50% Matrigel and 5 x 106 cells per mouse were injected subcutaneously into the flank of 6–8 week oldSCID–beige female mice. The tumors were allowed to grow to approximately 200 mm3, at which time mice were allocated by tumorvolume into study groups (n = 10 mice/ group) so that the mean tumor volumes of the groups were statistically similar. Mice werethen entered into the dosing phase of the study and tumor volumes were recorded 2 times per week. The effect of a treatment ontumor growth inhibition was determined as %TGI = mean tumor volume of control group–mean tumor volume of treatment group/tumor volume of treatment control group x 100. A–366 was formulated for delivery by osmotic mini–pump in 98% PEG–400 and 2%Tween–80.
References:
[1]. Pappano WN, et al. The Histone Methyltransferase Inhibitor A–366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia. PLoS One. 2015 Jul 6;
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10(7):e0131716.
Caution: Product has not been fully validated for medical applications. For research use only.
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