3-Deazaneplanocin A

Epigenetic modifier; Inhibits histone EZH2 lysine methyltransferase

3-Deazaneplanocin A

Epigenetic modifier; Inhibits histone EZH2 lysine methyltransferase

From: 205 USD
Catalog #
72322_C
Epigenetic modifier; Inhibits histone EZH2 lysine methyltransferase

Overview

Deazaneplanocin A (DZNep) is an inhibitor of lysine methyltransferases, particularly EZH2. DZNep therefore acts as an epigenetic modifier, specifically inhibiting the trimethylation of Histone 3, Lysine 27, by depleting levels of EZH2. (Miranda et al., Tan et al., Tseng et al.)

REPROGRAMMING
· Enables chemical reprogramming (without genetic factors) of mouse embryonic fibroblasts to induced pluripotent stem (iPS) cells, in combination with CHIR99021, Forskolin, Valproic Acid, Tranylcypromine, and E-616452, by increasing OCT4 expression at later stages of reprogramming (Hou et al.).
· Reactivation of XIST-dependent inactive X chromosomes in human embryonic stem cells (Diaz Perez et al.).

CANCER RESEARCH
· Inhibits self-renewal of glioblastoma multiforme cancer stem cells (Suva et al.).
· Inhibits survival of acute myeloid leukemia blast cells, in combination with a histone deacetylase inhibitor (Fiskus et al.).
Alternative Names
DZNep; NSC 617989
Cell Type
Cancer Cells and Cell Lines, Leukemia/Lymphoma Cells, Pluripotent Stem Cells
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Reprogramming
Area of Interest
Cancer, Stem Cell Biology
CAS Number
102052-95-9
Chemical Formula
C₁₂H₁₄N₄O₃
Molecular Weight
262.3 g/mol
Purity
≥ 97%
Pathway
Epigenetic
Target
Histone Methyltransferase

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Catalog #
72322, 72324
Lot #
All
Language
English
Document Type
Safety Data Sheet
Catalog #
72322, 72324
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Publications (7)

Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Hou P et al. Science (New York, N.Y.) 2013 AUG

Abstract

Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous master genes" are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications."
Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin. Diaz Perez SV et al. Human molecular genetics 2012 FEB

Abstract

Human embryonic stem cells (hESCs) are pluripotent cell types derived from the inner cell mass of human blastocysts. Recent data indicate that the majority of established female XX hESC lines have undergone X chromosome inactivation (XCI) prior to differentiation, and XCI of hESCs can be either XIST-dependent (class II) or XIST-independent (class III). XCI of female hESCs precludes the use of XX hESCs as a cell-based model for examining mechanisms of XCI, and will be a challenge for studying X-linked diseases unless strategies are developed to reactivate the inactive X. In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate and 3-deazaneplanocin A (DZNep). Our data demonstrate that successful reprogramming can occur from the XIST-dependent class II nuclear state but not class III nuclear state. To determine whether these small molecules prevent XCI, we derived six new hESC lines under normoxic conditions (UCLA1-UCLA6). We show that class I nuclei are present within the first 20 passages of hESC derivation prior to cryopreservation, and that supplementation with either sodium butyrate or DZNep preserve class I nuclei in the self-renewing state. Together, our data demonstrate that self-renewal and survival of class I nuclei are compatible with normoxic hESC derivation, and that chemical supplementation after derivation provides a strategy to prevent epigenetic progression and retain nuclei with two active X chromosomes in the self-renewing state.
Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Fiskus W et al. Blood 2009 SEP

Abstract

The polycomb repressive complex (PRC) 2 contains 3 core proteins, EZH2, SUZ12, and EED, in which the SET (suppressor of variegation-enhancer of zeste-trithorax) domain of EZH2 mediates the histone methyltransferase activity. This induces trimethylation of lysine 27 on histone H3, regulates the expression of HOX genes, and promotes proliferation and aggressiveness of neoplastic cells. In this study, we demonstrate that treatment with the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) depletes EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the cultured human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cells and in primary AML cells. DZNep treatment induced p16, p21, p27, and FBXO32 while depleting cyclin E and HOXA9 levels. Similar findings were observed after treatment with small interfering RNA to EZH2. In addition, DZNep treatment induced apoptosis in cultured and primary AML cells. Furthermore, compared with treatment with each agent alone, cotreatment with DZNep and the pan-histone deacetylase inhibitor panobinostat caused more depletion of EZH2, induced more apoptosis of AML, but not normal CD34(+) bone marrow progenitor cells, and significantly improved survival of nonobese diabetic/severe combined immunodeficiency mice with HL-60 leukemia. These findings indicate that the combination of DZNep and panobinostat is effective and relatively selective epigenetic therapy against AML cells.

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