Pinometostat (EPZ5676)

Catalog No.S7062

For research use only.

Pinometostat (EPZ5676) 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, inhibits H3K79 methylation in tumor. Phase 1.

Pinometostat (EPZ5676) Chemical Structure

CAS No. 1380288-87-8

Selleck's Pinometostat (EPZ5676) has been cited by 37 publications

Purity & Quality Control

Choose Selective Histone Methyltransferase Inhibitors

Biological Activity

Description Pinometostat (EPZ5676) 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, inhibits H3K79 methylation in tumor. Phase 1.
Targets
DOT1L [1]
(Cell-free assay)
80 pM(Ki)
In vitro

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.

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MV4-11 MlTxSpVv[3Srb36gZZN{[Xl? M3XvWlQh\GG7cx?= Mk\lTY5pcWKrdHnvckBw\iCGT2SxUEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiZYjwdoV{e2mwZzDNUGwuSUZ2IHHzd4V{e2WmIHHzJJJm\HWldHnvckBw\iCKM1u3PY1mOiCuZY\lcEBi\nSncjC0JIRigXNiYomgSWxKW0FibXX0bI9l NH;Ld|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUSwOlg2Oyd-MkW0NFY5PTN:L3G+
MOLM13 M{fkNXBzd2yrZnXyZZRqd25iYYPzZZk> MoX0RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCPT1zNNVMh[2WubIOgZ49vfGGrbnnu[{BOVExvQV[5MEBGSzVyPUSgcm0> M4DHflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEe5OFY{Lz5{M{i3PVQ3OzxxYU6=
MV4-11 MWrQdo9tcW[ncnH0bY9vKGG|c3H5 MXLBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2YND2xNUBk\WyuczDjc451[WmwaX7nJG1NVC2DRkSsJGVEPTB;NDDuUS=> MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5OUS2N{c,OjN6N{m0OlM9N2F-
THP1 MmDJVJJwdGmoZYLheIlwdiCjc4PhfS=> MXrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFSKUEGgZ4VtdHNiY3;ueIFqdmmwZzDNUGwuSUZ7LDDFR|UxRTRibl2= NETtbVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3PVQ3Oyd-MkO4O|k1PjN:L3G+
HeLa M2TrdmZ2dmO2aX;uJIF{e2G7 NH;zWFQ4OiCqcoO= NH7GXnNKdmirYnn0bY9vKG:oIFTPWFFNKGmwIHj1cYFvKEinTHGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEh|S{e5cYUzKGyndnXsJIFnfGW{IEeyJIhzeyCkeTDFUGlUSSxiSVO1NEA:KDBwMEC3JO69VS5? NWPtWnZjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkizN|c{OjdpPkK4N|M4OzJ5PD;hQi=>
MV4-11 M2PHXWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NH73e5I3KGi{cx?= NWjHZlMySW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhcGG{Yn;ybY5oKE2OTD3BSlQhfHKnYYTl[EBnd3JiNjDodpMhdWWjc4Xy[YQh[W[2ZYKgPEBl[Xm|IHL5JGNmdGy2aYTldk1IdG9icnXh[4VvfCCkYYPl[EBie3OjeTygTWM2OCB;IECuNFE2KM7:TT6= NHPEbZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEOzO|MzPyd-MkizN|c{Ojd:L3G+
MOLM13 NUm2NnY6TnWwY4Tpc44h[XO|YYm= MVS3NkBpenN? NH3zNoNKdmirYnn0bY9vKG:oIFTPWFFNKGmwIHj1cYFvKE2RTF2xN{Bk\WyuczDhd5Nme3OnZDDhd{B{fXCycnXzd4lwdiCxZjDIc5hCQSCpZX7lJIFnfGW{IEeyJIhzeyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEmFNUCgQUAxNjB3MjFOwG0v NHXFN3A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEOzO|MzPyd-MkizN|c{Ojd:L3G+
Assay
Methods Test Index PMID
Western blot p-p65 / p65 / NFATc1 ; CDK6 / BCL11A / Bcl-2 / RUNX1 / MEF2C / H3K79me3 / H4 29348610 28076791
Immunofluorescence NFATc1 29348610
In vivo EPZ-5676 continuously intravenous infusion for 21 days to xenograft model of MLL-rearranged leukemia, leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. No significant weight loss or obvious toxicity is observed in rats treated with EPZ-5676 during efficacy study.

Protocol (from reference)

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 562.71
Formula

C30H42N8O3

CAS No. 1380288-87-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)N(CC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02141828 Completed Drug: EPZ-5676 Leukemia|Acute Myeloid Leukemia|Acute Lymphocytic Leukemia|Acute Leukemias Epizyme Inc.|Celgene Corporation May 2014 Phase 1
NCT01684150 Completed Drug: EPZ-5676 Acute Myeloid Leukemia|Acute Lymphoblastic Leukemia|Myelodysplastic Syndrome|Myeloproliferative Disorders Epizyme Inc.|Celgene September 2012 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Is the vehicle 30% PEG400/0.5% Tween80/5% propylene glycol recommended for in vivo use?

Answer:
S7062 EPZ-5676 in 30% PEG400/0.5% Tween80/5% propylene glycol at 30 mg/ml is a suspension. For injection, 2% DMSO/30% PEG 300/5% Tween 80/ddH2O at 5 mg/ml is suitable.

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