product name EPZ5676
Description: EPZ-5676, also known as pinometostat, is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with Ki of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, it inhibits H3K79 methylation in tumor. EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes.
References: Blood. 2013 Aug 8;122(6):1017-25.
562.71
Formula
C30H42N8O3
CAS No.
1380288-87-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (177.71mM)
Water: <1 mg/mL
Ethanol: 92 mg/mL (163.5 mM)
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL
Synonyms
Pinometostat.
other peoduct :
| In Vitro |
In vitro activity: EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. EPZ-5676 inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM. Kinase Assay: The enzyme inhibition constant (Ki) value for EPZ5676 was determined by fitting inhibition data to the Morrison quadratic equation. Residence time for EPZ5676 was calculated as the reciprocal of the enzymatic-ligand dissociation rate, determined by surface plasmon resonance. Cell Assay: EPZ5676 potently inhibited MV4-11 cell proliferation with an IC50 value of 3.5 nM. Antiproliferative activity was realized after 4 days and was most clear after 7 days of EPZ-5676 treatment. |
|---|---|
| In Vivo | In nude rats bearing MV4-11 xenografts, EPZ5676 caused complete tumor regressions that were sustained well beyond the compound infusion period with no significant weight loss or signs of toxicity. |
| Animal model | Nude rats bearing MV4-11 xenografts |
| Formulation & Dosage | 35, 67 or 70 mg/kg/day; i.v. |
| References | Blood. 2013 Aug 8;122(6):1017-25 |
