WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406244
CAS#: 1338466-77-5
Description: EPZ004777 is a potent, selective inhibitor of DOT1L. Treatment of mixed lineage leukemia (MLL) cells with EPZ004777 selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. Exposure of leukemic cells to EPZ004777 results in selective killing of those cells bearing the MLL gene translocation, with little effect on non-MLL-translocated cells. Finally, in vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model. These results provide compelling support for DOT1L inhibition as a basis for targeted therapeutics against MLL.
Hodoodo Cat#: H406244
Name: EPZ004777
CAS#: 1338466-77-5
Chemical Formula: C28H41N7O4
Exact Mass: 539.32
Molecular Weight: 539.670
Elemental Analysis: C, 62.32; H, 7.66; N, 18.17; O, 11.86
Synonym: EPZ004777; EPZ 004777; EPZ-004777.
IUPAC/Chemical Name: 1-(3-((((2R,3S,4R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
InChi Key: WXRGFPHDRFQODR-ICLZECGLSA-N
InChi Code: InChI=1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1
SMILES Code: O=C(NC1=CC=C(C(C)(C)C)C=C1)NCCCN(C[C@H]2O[C@@H](N3C=CC4=C(N)N=CN=C43)[C@H](O)[C@@H]2O)C(C)C
Appearance: 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: >5 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
More Info:
| Biological target: | EPZ004777 is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM. |
| In vitro activity: | Different concentrations of EPZ (EPZ004777) were used in HK-2 cells subjected to 12 hrs of hypoxia and 24 hrs of reoxygenation. The results of PCR and WB indicated that EPZ could reduce the expression of α-SMA, vimentin, and fibronectin in a dose-dependent manner (Figure 5A and B). Reference: Drug Des Devel Ther. 2019; 13: 4375–4387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939406/ |
| In vivo activity: | Similarly, the inhibition of Dot1l with either EPZ (EPZ004777) or small interfering RNA (siRNA) showed an inhibitory effect on HSV-1-induced oxidative stress and inflammation in HCE cells. Reference: Oxid Med Cell Longev. 2021 Feb 15;2021:6612689. https://pubmed.ncbi.nlm.nih.gov/33628364/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 84.7 | 156.87 | |
| Ethanol | 77.0 | 142.66 |
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 |
| Formulation protocol: | 1. Wan S, Zhou Y, Huang Q, Yang Y. Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress. Oxid Med Cell Longev. 2021 Feb 15;2021:6612689. doi: 10.1155/2021/6612689. PMID: 33628364; PMCID: PMC7899779. 2. Yang C, Chen Z, Yu H, Liu X. Inhibition of Disruptor of Telomeric Silencing 1-Like Alleviated Renal Ischemia and Reperfusion Injury-Induced Fibrosis by Blocking PI3K/AKT-Mediated Oxidative Stress. Drug Des Devel Ther. 2019 Dec 27;13:4375-4387. doi: 10.2147/DDDT.S224909. PMID: 31920287; PMCID: PMC6939406. 3. Yang L, Lei Q, Li L, Yang J, Dong Z, Cui H. Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenetics. 2019 Dec 30;11(1):199. doi: 10.1186/s13148-019-0778-y. PMID: 31888761; PMCID: PMC6937672. |
| In vitro protocol: | 1. Wan S, Zhou Y, Huang Q, Yang Y. Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress. Oxid Med Cell Longev. 2021 Feb 15;2021:6612689. doi: 10.1155/2021/6612689. PMID: 33628364; PMCID: PMC7899779. |
| In vivo protocol: | 1. Yang C, Chen Z, Yu H, Liu X. Inhibition of Disruptor of Telomeric Silencing 1-Like Alleviated Renal Ischemia and Reperfusion Injury-Induced Fibrosis by Blocking PI3K/AKT-Mediated Oxidative Stress. Drug Des Devel Ther. 2019 Dec 27;13:4375-4387. doi: 10.2147/DDDT.S224909. PMID: 31920287; PMCID: PMC6939406. 2. Yang L, Lei Q, Li L, Yang J, Dong Z, Cui H. Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenetics. 2019 Dec 30;11(1):199. doi: 10.1186/s13148-019-0778-y. PMID: 31888761; PMCID: PMC6937672. |
1: Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288. doi: 10.1038/ncomms2304. PubMed PMID: 23250418.
2: Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C, Olhava EJ, Daigle SR, Richon VM, Pollock RM, Armstrong SA. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2012 Nov 9. doi: 10.1038/leu.2012.327. [Epub ahead of print] PubMed PMID: 23138183.
3: Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tseng JC, Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65. doi: 10.1016/j.ccr.2011.06.009. PubMed PMID: 21741596.
