Synonym
EPZ005687; EPZ 005687; EPZ-005687; EPZ5687; EPZ-5687; EPZ 5687.
IUPAC/Chemical Name
1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-(morpholinomethyl)phenyl)-1H-indazole-4-carboxamide.
InChi Key
ZOIBZSZLMJDVDQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C32H37N5O3/c1-21-15-22(2)35-32(39)28(21)18-33-31(38)27-16-25(17-30-29(27)19-34-37(30)26-5-3-4-6-26)24-9-7-23(8-10-24)20-36-11-13-40-14-12-36/h7-10,15-17,19,26H,3-6,11-14,18,20H2,1-2H3,(H,33,38)(H,35,39)
SMILES Code
O=C(C1=CC(C2=CC=C(CN3CCOCC3)C=C2)=CC4=C1C=NN4C5CCCC5)NCC6=C(C)C=C(C)NC6=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
In vitro activity:
The U937 cells and normal CD34⁺ cells were treated with different concentration of EPZ005687 at different time points. The apoptosis rate was determined by Annexin V/PI staining. The cell proliferation and cell cycle was determined using WST-1 assay and 7-AAD assay, respectively. The activity of H3K27 methylation was detected by chemiluminescent immunoassay. The results showed that the EPZ005687 induced an obvious apoptosis of U937 cells. The apoptotic rate was 3.96% ± 0.79%,5.74% ± 0.73%,13.34% ± 1.77% and 25.24% ± 2.55% in U937 cells treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 for 48 hours, respectively. However, EPZ005687 had rare effect on normal bone marrow(NBM) CD34⁺ cells. The apoptotic rate was 3.64% ± 0.62%,4.28% ± 0.99%,6.18% ± 1.19% and 7.56% ± 1.34% after U937 cells were treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 for 48 hours, respectively. EPZ005687 inhibited obviously the proliferation of U937 cells but had weak effect on the proliferation of NBMCD34⁺ cells. The inhibitory effect of EPZ005687 on U937 cells was time-dependent after treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 from 12 to 96 hours. EPZ005687 induced G1 phase blocking (G1%, 64.18% ± 13.27% vs 49.43% ± 12.54%) and decreased the percentage of cells in S phase (9.67% ± 2.61% vs15.26% ± 5.58%) in U937 cells. However, EPZ005687 had no effect on the cell cycle of NBMCD34⁺ cells. In addition, EPZ005687 produced obviously depletion of H3K27 methylation in U937 cells (P < 0.05), but hardly had effect on the H3K27 methylation of NBMCD34⁺ cells. It is concluded that the EPZ005687 inhibites proliferation, induces apoptosis and cell cycle blocking in G1 phase in leukemia cells. This agent may have potential value in clinical application.
Reference: Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Dec;22(6):1561-6.
In vivo activity:
To assess the biological impact of EZH2 on the development of pulmonary hypertension, we first measured the RVSP as an indicator of pulmonary artery pressure in spontaneously breathing mice, following sham control and TAC operation, EPZ005687 or DMSO was injected peritoneally as described in methods. On day 28 after TAC, the RVSBP was markedly higher in the TAC group than in the sham control group (Figures 2(a) and 2(d)). Besides, as shown in Figures 2(b) and 2(c), ratios of RV and lung weight to body weight were significantly increased 2.1-fold and 2.6-fold in TAC mice compared to sham control mice, respectively. EPZ005687 treatment significantly alleviated the further increase of RVSBP, ratios of LV and lung weight to body weight, respectively. These findings suggest that EPZ005687 treatment might have a prominent role in protecting against TAC-induced PAH and RV hypertrophy in vivo.
Reference: Can Respir J. 2018 Feb 28;2018:9174926. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29854032/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
9.4 |
17.42 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
539.67
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
In vitro protocol:
1. Tang SH, Pei RZ, Ma JX, Zhang PS, Liu XH, DU XH, Chen D, Sha KY, Cao JJ, Li SY. [Effects of H3K27 methylation inhibitor EPZ005687 on apoptosis, proliferation and cell cycle of U937 cells and normal CD34 positive cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Dec;22(6):1561-6. Chinese. doi: 10.7534/j.issn.1009-2137.2014.06.012. PMID: 25543475.
In vivo protocol:
1. Shi ZL, Fang K, Li ZH, Ren DH, Zhang JY, Sun J. EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice. Can Respir J. 2018 Feb 28;2018:9174926. doi: 10.1155/2018/9174926. PMID: 29854032; PMCID: PMC5960552.
1: Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, Scott MP, Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM, Kuntz KW. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6. doi: 10.1038/nchembio.1084. Epub 2012 Sep 30. PubMed PMID: 23023262.
