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EPZ5676 DOT1L inhibitor,potent and SAM competitive

Catalog No.A4166
Size Price Stock Qty
10mM (in 1mL DMSO)
$175.00
In stock
10mg
$170.00
In stock
50mg
$590.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

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Sample solution is provided at 25 µL, 10mM.

Product Citations

1. Kim MS, Cho HI, et al. "JIB-04, A Small Molecule Histone Demethylase Inhibitor, Selectively Targets Colorectal Cancer Stem Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway." Sci Rep. 2018 Apr 26;8(1):6611. PMID:29700375

Quality Control

Chemical structure

EPZ5676

Biological Activity

Description EPZ5676 is a potent and selective inhibitor of DOT1L methyltransferase with Ki value of 80 pM.
Targets DOT1L          
IC50 80 pM (Ki)          

Protocol

Kinase experiment [1]:

Biochemical enzyme inhibition assays

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 experiment [1]:

Cell lines

MV4-11 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

0.0005 ~ 10 μM; 14 days

Applications

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.

Animal experiment [1]:

Animal models

Nude rats bearing MV4-11 xenografts

Dosage form

35, 67 or 70 mg/kg/day; i.v.; for 21 days

Applications

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.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025.

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Chemical Properties

Cas No. 1380288-87-8 SDF Download SDF
Synonyms N/A
Chemical Name (2R,3S,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[2-(6-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl]-propan-2-ylamino]methyl]oxolane-3,4-diol
Canonical SMILES CC(C)N(CC1C(C(C(O1)N2C=NC3=C2N=CN=C3N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C
Formula C30H42N8O3 M.Wt 562.71
Solubility >28.2mg/mL in DMSO Storage Store at -20°C
Shipping Condition Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Background

EPZ5676 is a potent inhibitor of DOT1L histone methyltransferase, according to X-ray crystallographic analysis, that occupies the S-adenosyl methionine (SAM) binding pocket of DOT1L and induces conformational changes in DOT1L resulting in the opening of a hydrophobic pocket beyond the amino acid portion of SAM. EPZ5676 selectively inhibits DOTIL with a value of 50% inhibition concentration IC50 of 0.8 nM, which is 37000-fold greater in selectivity than other methyltransferases, including CARM1, EHMT1/2, EZH1/2, PRMT1/2/5/6/8, SETD7, SMYD2/3, and WHSC1/1L1. EPZ5676 has been investigated for the treatment of MLL-rearranged leukemia in multiple studies where results have shown that EPZ5676 inhibits H3K79 methylation and the expression of MLL-fusion target gene and potently kills acute leukemia cell lines bearing MLL translocation.

Reference

Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-1025.