Millipore Sigma Vibrant Logo
Attention: We have moved. Merck Millipore products are no longer available for purchase on MerckMillipore.com.Learn More

532282 DOT1L Inhibitor, EPZ004777 - CAS 1338466-77-5 - Calbiochem

EPZ004777, DOT1L Inhibitor

MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: 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), EPZ4777, HMTase Inhibitor XVI

Primary Target: DOT1L
View Products on Sigmaaldrich.com
532282
  
Purchase on Sigma-Aldrich

Overview

Replacement Information

Key Spec Table

CAS #Empirical Formula
1338466-77-5C₂₈H₄₁N₇O₄
Description
Overview

This product has been discontinued.



A cell-permeable, non-toxic, a near chemical derivative of S-adenosylmethionine (SAM) that competitively binds to the SAM-binding pocket of DOT1L and inhibits its activity in a reversible manner (IC50 = 400 pM; Ki = 300 pM). Shown to inhibit the methylation of cellular H3K79 in MLL cells and block the expression of leukemogenic genes. Displays excellent selectivity over other histone methyltransferases PRMT5 (IC50 = 521 nM), CARM1, EHMT2, EZH1, EZH2, PRMT1, PRMT8, SETD7 and WHSC1 (IC50 > 50 µM). Inhibits the proliferation of MV4-1, MOLM-13, KOPN-8 cells (IC50 = 170, 720, and 620 nM, respectively) and suppresses the growth of MV4-11 xenografts in nude mice model (50 mg/ml, s.c. minipump infusion). Blocks the cell cycle at G0/G1 phase and induces apoptotic cell death by activating caspase 3/7. Also shown to accelerate reprogramming of somatic cells into induced pluripotent stem cells.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Catalogue Number532282
Brand Family Calbiochem®
Synonyms1-(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), EPZ4777, HMTase Inhibitor XVI
References
ReferencesDaigle, S.R., et al. 2013. Blood. 122, 1017.
Yu, W., et al. 2012. Nat. Commun. 3, 1288.
Daigle, S.R., et al. 2011. Cancer Cell. 20, 53.
Product Information
CAS number1338466-77-5
FormWhite powder
Hill FormulaC₂₈H₄₁N₇O₄
Chemical formulaC₂₈H₄₁N₇O₄
Hygroscopic Hygroscopic
ReversibleY
Quality LevelMQ100
Applications
Biological Information
Primary TargetDOT1L
Primary Target IC<sub>50</sub>400 pM
Primary Target K<sub>i</sub>300 pM
Purity≥97% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage -20°C
Protect from Light Protect from light
Hygroscopic Hygroscopic
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Catalogue Number GTIN
532282 0

Documentation

DOT1L Inhibitor, EPZ004777 - CAS 1338466-77-5 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

References

Reference overview
Daigle, S.R., et al. 2013. Blood. 122, 1017.
Yu, W., et al. 2012. Nat. Commun. 3, 1288.
Daigle, S.R., et al. 2011. Cancer Cell. 20, 53.

Brochure

Title
NPI Flyer- Epigenetics and Nuclear Function Feature
New Products - Antibodies, Small Molecule, Inhibitors

Technical Info

Title
White Paper: Further considerations of antibody validation and usage.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision19-December-2014 JSW
Synonyms1-(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), EPZ4777, HMTase Inhibitor XVI
DescriptionA cell-permeable S-adenosylmethionine (AdoMet/SAM) structural derivative that potently inhibits DOT1L methyltransferase activity (IC50 = 400 pM) in a SAM-competitive (Ki = 300 pM) manner via a 1:1 stoichiometric interaction (KD = 250 pM), not only blocking DOT1L SAM-binding site with its deazaadenosine moiety, but also disrupting the overall structural integrity of the catalytic pocket with its tert-butylphenyl moiety, while inhibiting PRMT5 only at much higher concentrations (IC50 = 521 nM or 25 µM, respectively, using free or MEP50-complexed PRMT5) and exhibiting little potency against CARM1, EHMT2, EZH1, EZH2, PRMT1, PRMT8, SETD7, or WHSC1 even at a high concentration of 50 µM. Although EPZ004777 effectively inhibits cellular H3K79 methylation regardless of MLL translocation status (ICmax ~3 µM post 4 d treatment in MV4-11, MOLM-13, and Jurkat cells with MLL-AF4, MLL-AF9, and no MLL rearrangement, respectively), the viability of MLL rearranged cells are more susceptible to EPZ004777 treatment (IC50 = 0.62 to 6.74 µM in cultures with MLL-AF4, MLL-AF9, or MLL-ENL fusion; GI50 =13.9 µM to no inhibition at 50 µM in cultures with no MLL rearrangement; by Guava ViaCount Assay/4000-0040 at the end of 14 to 18 treatment period; cells split with fresh media/inhibitor every 3-4 d) due to effective transcription blockage of MLL fusion target genes (IC50 ~700 nM in reducing HOXA9 & MEIS1 mRNA levels in MV411 & MOLM-13 cultures). Despite poor pharmacokinetic properties, continuous EPZ004777 infusion via subcutaneously implanted osmotic pumps (100 mg/mL & 150 mg/mL to achieve steady state plasma drug conc of 0.64 & 0.84 µM, respectively) is reported to significantly extend the survival of NSG mice received MV4-11 cells via tail vein injection (100% death on d11 or d17 post 14 d vehicle or drug infusion period, respectively).
FormWhite powder
Intert gas (Yes/No) Packaged under inert gas
CAS number1338466-77-5
Chemical formulaC₂₈H₄₁N₇O₄
Purity≥97% by HPLC
SolubilityDMSO (50 mg/ml). Insoluble in H₂O. Use only fresh DMSO for reconstitution.
Storage Protect from light
-20°C
Hygroscopic
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity Standard Handling
ReferencesDaigle, S.R., et al. 2013. Blood. 122, 1017.
Yu, W., et al. 2012. Nat. Commun. 3, 1288.
Daigle, S.R., et al. 2011. Cancer Cell. 20, 53.