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AB146152

UNC1999, EZH2 methyltransferase inhibitor

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(2 Publications)

MW 569.7 Da, Purity >98%. Potent, selective cell-permeable dual inhibitor of EZH2 and EZH1 methyltransferase inhibitor (IC50 = 45 nM and 2 nM respectively) (Konze et al. ). Inhibits H3K27 methylation (IC50 = 124 nM, MCF10A cells). Competitive with the cofactor SAM, and non-competitive with the peptide substrate. Inhibition of EZH2 with UNC1999 enhanced the efficacy of gefitinib in suppressing the proliferation of colon cancer cells (Katona et al.). It suppresses global H3K27 trimethylation/demethylation and inhibits the growth of mixed lineage leukemia (MLL)-rearranged leukemia cells ( Xu et al.). Orally bioavailable.

View Alternative Names

ENX-1, ENX-2, EZH1_HUMAN, EZH2_HUMAN, EZH2b, Enhancer of zeste 2, Enhancer of zeste homolog 1, Enhancer of zeste homolog 1 (Drosophila), Enhancer of zeste homolog 2, Enhancer of zeste homolog 2 (Drosophila), Enhancer of zeste, Drosophila, homolog 2, Enx 1h, Histone-lysine N-methyltransferase EZH1, Histone-lysine N-methyltransferase EZH2, KMT 6, KMT6A, Lysine N-methyltransferase 6, MGC9169, WVS, WVS2, enhancer of zeste 2 polycomb repressive complex 2 subunit

1 Images
Chemical Structure - UNC1999, EZH2 methyltransferase inhibitor (AB146152)
  • Chemical Structure

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Chemical Structure - UNC1999, EZH2 methyltransferase inhibitor (AB146152)

2D chemical structure image of ab146152, UNC1999, EZH2 methyltransferase inhibitor

Key facts

CAS number

1431612-23-5

Purity

>98%

Form

Solid

form

Molecular weight

569.7 Da

Molecular formula

C<sub>3</sub><sub>3</sub>H<sub>4</sub><sub>3</sub>N<sub>7</sub>O<sub>2</sub>

PubChem

72551585

Nature

Synthetic

Biochemical name

N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-1-propan-2-yl-6-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]indazole-4-carboxamide

Biological description

Potent, selective cell-permeable dual inhibitor of EZH2 and EZH1 methyltransferase inhibitor (IC50 = 45 nM and 2 nM respectively) (Konze et al. ). Inhibits H3K27 methylation (IC50 = 124 nM, MCF10A cells). Competitive with the cofactor SAM, and non-competitive with the peptide substrate. Inhibition of EZH2 with UNC1999 enhanced the efficacy of gefitinib in suppressing the proliferation of colon cancer cells (Katona et al.). It suppresses global H3K27 trimethylation/demethylation and inhibits the growth of mixed lineage leukemia (MLL)-rearranged leukemia cells ( Xu et al.). Orally bioavailable.

Canonical smiles

CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CN=C(C=C4)N5CCN(CC5)C(C)C)C(C)C

InChi

InChI=1S/C33H43N7O2/c1-7-8-24-15-23(6)37-33(42)28(24)19-35-32(41)27-16-26(17-30-29(27)20-36-40(30)22(4)5)25-9-10-31(34-18-25)39-13-11-38(12-14-39)21(2)3/h9-10,15-18,20-22H,7-8,11-14,19H2,1-6H3,(H,35,41)(H,37,42)

InChiKey

DPJNKUOXBZSZAI-UHFFFAOYSA-N

IUPAC Name

N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-1-propan-2-yl-6-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]indazole-4-carboxamide

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Properties and storage information

Shipped at conditions
Ambient - Can Ship with Ice
Appropriate short-term storage conditions
-20°C
Appropriate long-term storage conditions
-20°C
Storage information
Store under desiccating conditions|The product can be stored for up to 12 months
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Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

KMT6 also known as EZH2 (Enhancer of Zeste Homolog 2) is a protein that functions as a histone methyltransferase. It catalyzes the methylation of histone H3 on lysine 27 (H3K27) a modification associated with gene silencing. EZH2 is a component of the Polycomb Repressive Complex 2 (PRC2) which plays an important role in chromatin remodeling and transcriptional repression. The EZH2 protein has a molecular weight of approximately 87 kDa and its gene is located on chromosome 7. In terms of expression EZH2 is found in various tissues but is notably abundant in growing and dividing cells.
Biological function summary

EZH2 plays a central role in regulating gene expression during development and differentiation. It is a core component of the PRC2 complex which includes other proteins such as EED and SUZ12. Through its catalytic activity EZH2 contributes to the maintenance of the transcriptionally repressed state of genes influencing processes such as cell identity and proliferation. In many cell types EZH2-mediated gene silencing is necessary for normal development and dysregulation can lead to aberrant cellular processes.

Pathways

EZH2 participates in key regulatory networks notably the Wnt signaling pathway and the p53 pathway. Within the Wnt pathway EZH2's activity contributes to controlling gene expression that influences cellular differentiation and proliferation. Meanwhile interaction with the p53 pathway can impact the cellular response to stress and DNA damage highlighting EZH2’s regulatory dimension. Other proteins like β-catenin in the Wnt pathway interact with EZH2 reflecting its integration in these complex signaling networks.

EZH2 has been linked to cancer and other proliferative diseases. Overexpression or mutation of EZH2 is frequently observed in cancers such as prostate and breast cancer where it contributes to unchecked cell growth and tumor progression. In these contexts proteins like p53 can interact abnormally with EZH2 leading to failure in tumor suppression mechanisms. Additionally deregulated EZH2 activity is implicated in certain developmental disorders highlighting its broader impact on cellular and organismal homeostasis.
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Product protocols

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Publications (2)

Recent publications for all applications. Explore the full list and refine your search

Nature cell biology 24:858-871 PubMed35697783

2022

Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction.

Applications

Unspecified application

Species

Unspecified reactive species

Dick W Zijlmans,Irene Talon,Sigrid Verhelst,Adam Bendall,Karlien Van Nerum,Alok Javali,Andrew A Malcolm,Sam S F A van Knippenberg,Laura Biggins,San Kit To,Adrian Janiszewski,Danielle Admiraal,Ruth Knops,Nikky Corthout,Bradley P Balaton,Grigorios Georgolopoulos,Amitesh Panda,Natarajan V Bhanu,Amanda J Collier,Charlene Fabian,Ryan N Allsop,Joel Chappell,Thi Xuan Ai Pham,Michael Oberhuemer,Cankat Ertekin,Lotte Vanheer,Paraskevi Athanasouli,Frederic Lluis,Dieter Deforce,Joop H Jansen,Benjamin A Garcia,Michiel Vermeulen,Nicolas Rivron,Maarten Dhaenens,Hendrik Marks,Peter J Rugg-Gunn,Vincent Pasque

Nature genetics 54:459-468 PubMed35410383

2022

H3K27me3 conditions chemotolerance in triple-negative breast cancer.

Applications

Unspecified application

Species

Unspecified reactive species

Justine Marsolier,Pacôme Prompsy,Adeline Durand,Anne-Marie Lyne,Camille Landragin,Amandine Trouchet,Sabrina Tenreira Bento,Almut Eisele,Sophie Foulon,Léa Baudre,Kevin Grosselin,Mylène Bohec,Sylvain Baulande,Ahmed Dahmani,Laura Sourd,Eric Letouzé,Anne-Vincent Salomon,Elisabetta Marangoni,Leïla Perié,Céline Vallot
View all publications
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