| Identification | Back Directory | [Name]
EPZ011969 | [CAS]
1598383-40-4 | [Synonyms]
CS-2079
CS-1609
EPZ011969
EPZ011989
EPZ011989;EPZ-011989
N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl((1r,4r)-4-((2-methoxyethyl)(methyl)amino)cyclohexyl)amino)-2-methyl-5-(3-morpholinoprop-1-ynyl)benzamide
N-((4,6-DIMETHYL-2-OXO-1,2-DIHYDROPYRIDIN-3-YL)METHYL)-3-(ETHYL((TRANS)-4-((2-METHOXYETHYL)(METHYL)AMINO)CYCLOHEXYL)AMINO)-2-METHYL-5-(3-MORPHOLINOPROP-1-YN-1-YL)BENZAMIDE
N-[(1,2-Dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-[ethyl[trans-4-[(2-methoxyethyl)methylamino]cyclohexyl]amino]-2-methyl-5-[3-(4-morpholinyl)-1-propyn-1-yl]benzamide
Benzamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-[ethyl[trans-4-[(2-methoxyethyl)methylamino]cyclohexyl]amino]-2-methyl-5-[3-(4-morpholinyl)-1-propyn-1-yl]- | [Molecular Formula]
C35H51N5O4 | [MDL Number]
MFCD28964159 | [MOL File]
1598383-40-4.mol | [Molecular Weight]
605.81 |
| Chemical Properties | Back Directory | [Boiling point ]
756.7±60.0 °C(Predicted) | [density ]
1.17±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:55.0(Max Conc. mg/mL);90.79(Max Conc. mM)
DMF:10.0(Max Conc. mg/mL);16.51(Max Conc. mM)
Ethanol:60.0(Max Conc. mg/mL);99.04(Max Conc. mM)
Ethanol:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);0.83(Max Conc. mM) | [form ]
A crystalline solid | [pka]
11.88±0.10(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
The lysine methyltransferase EZH2 (KMT6), part of polycomb repressive complex 2, catalyzes trimethylation of lysine 27 on histone H3 and is involved in proliferation and aggressive cell growth associated with neoplastic cells.1 EPZ011989 is an orally bioavailable EZH2 inhibitor with Ki values that are less than 3 nM for wild type and Tyr646 mutated EZH2.2 It displays 15-fold selectivity for EZH2 over EZH1 and is without effect against an array of other lysine methyltransferases.2 EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.2 | [Uses]
N-[(1,2-Dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-[ethyl[trans-4-[(2-methoxyethyl)methylamino]cyclohexyl]amino]-2-methyl-5-[3-(4-morpholinyl)-1-propyn-1-yl]-benzamide is used in biological studies as inhibitors of EZH2 histone methyltransferase for the treatment of cancer. | [in vivo]
EPZ011989 (oral; 30-1000 mg/kg; single or bid; for 7 days or 21 days) can elicit robust methyl mark inhibition and antitumor activity[1]. | Animal Model: | SCID mice[1] | | Dosage: | 125, 250, 500, and 1000 mg/kg | | Administration: | Oral; single, twice-daily (BID)for 7 days or twice-daily (BID)for 21 days | | Result: | Provided coverage over the LCC for 24 h (1000 mg/kg ), while the 250 and 500 mg/kg doses provided coverage over this value for approximately 8 h.
Observed complete ablation of the methyl mark by the end of day 7.
Showed robust tumor growth inhibition, methyl mark reduction and extended total and free plasma exposure time.
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| Animal Model: | Rat[1] | | Dosage: | 30, 100, and 300 mg/kg | | Administration: | Oral, single | | Result: | | dose (mg/kg) | route | t1/2 (h) | tmax (h) | Cmax (ng/mL) | AUCinf (h*ng/mL) | time above LCC (h) | | 30 | p.o. | 4.7 | 2 | 240 | 970 | 4 | | 100 | p.o. | 3.9 | 2.7 | 1600 | 5600 | 8 | | 300 | p.o. | 3.7 | 2.7 | 2900 | 10000 | 10 |
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| [IC 50]
EZH2 | [References]
[1] JEFFREY A. SIMON Carol A L. Roles of the EZH2 histone methyltransferase in cancer epigenetics[J]. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2008, 647 1: Pages 21-29. DOI: 10.1016/j.mrfmmm.2008.07.010
[2] JOHN E. CAMPBELL*. EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity[J]. ACS Medicinal Chemistry Letters, 2015, 6 5: 491-495. DOI: 10.1021/acsmedchemlett.5b00037 |
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