Abcam, ab269816, GSK126, EZH2 methyltransferase inhibitor

Size: 5mg / 10mg / 50mg
MW 526.7 Da. Potent inhibitor EZH2 methyltransferase inhibitor (K i = 93 pM). Selective (>150-fold) versus EZH1. Greater than 1000-fold selective against a panel of 20 other human methyltransferases including both SET-domain-containing and non-SET-domain-containing methyltransferases. Decreases global H3K27me3 levels. Inhibits B-cell lymphoma cell proliferation in vitro. Inhibits EZH2 mutant tumor growth in xenograft models. Reactivates silenced PRC2 target genes and inhibits the proliferation of EZH2 mutant DLBCL cell lines and corresponding xenografts mice. Literature suggests that GSK126 is a potential treatment for EZH2 mutant lymphoma (McCabe et al).
Key facts
CAS number:1346574-57-9,
Form:SolidSee storage information,
Molecular weight:526.7 Da,
Molecular formula:C31H38N6O2,
PubChem:68210102,
Nature:Synthetic,
Biochemical name:(S)-1-(sec-Butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide,
Biological description:Potent inhibitor EZH2 methyltransferase inhibitor (Ki = 93 pM). Selective (>150-fold) versus EZH1. Greater than 1000-fold selective against a panel of 20 other human methyltransferases including both SET-domain-containing and non-SET-domain-containing methyltransferases. Decreases global H3K27me3 levels. Inhibits B-cell lymphoma cell proliferation in vitro. Inhibits EZH2 mutant tumor growth in xenograft models. Reactivates silenced PRC2 target genes and inhibits the proliferation of EZH2 mutant DLBCL cell lines and corresponding xenografts mice. Literature suggests that GSK126 is a potential treatment for EZH2 mutant lymphoma (McCabe et al),
Canonical smiles:CCC(C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C,
Isomeric smiles:CC[C@H](C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C,
InChi:InChI=1S/C31H38N6O2/c1-6-22(5)37-18-20(3)29-25(30(38)34-17-26-19(2)13-21(4)35-31(26)39)14-24(15-27(29)37)23-7-8-28(33-16-23)36-11-9-32-10-12-36/h7-8,13-16,18,22,32H,6,9-12,17H2,1-5H3,(H,34,38)(H,35,39)/t22-/m0/s1,
InChiKey:FKSFKBQGSFSOSM-QFIPXVFZSA-N,
IUPAC Name:1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-(6-piperazin-1-ylpyridin-3-yl)indole-4-carboxamide

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

Supplementary Information:
This supplementary information is collated from multiple sources and compiled automatically.
The target KMT6 also known as EZH2 is an important player in the regulation of chromatin structure through its function as a methyltransferase. EZH2 along with EED and SUZ12 forms the core components of the Polycomb Repressive Complex 2 (PRC2). The molecular mass of the EZH2 protein is approximately 85 kDa. This protein is expressed in various tissues with notable presence in lymphoid tissues and the central nervous system. There exist numerous EZH2 inhibitors targeting this protein such as GSK126 which highlight its importance in biological processes and potential for therapeutic intervention.
Biological function summary
The PRC2 complex involving EZH2 EED and SUZ12 regulates gene expression by catalyzing the trimethylation of histone H3 on lysine 27 (H3K27me3) an important epigenetic marker for gene repression. The complex controls genes involved in development differentiation and proliferation. EZH2's activity is notably high in stem cells and proliferating cells due to its role in maintaining chromatin compaction and transcriptional silencing.
Pathways
The EZH2 protein and its associated PRC2 complex are elements of the epigenetic regulatory pathways controlling gene expression. They significantly impact the Wnt signaling pathway which influences embryonic development and cell growth. Additionally EZH2 interacts with other proteins such as histone deacetylases (HDACs) to facilitate tighter chromatin binding and gene silencing highlighting its role within the chromatin modification network.
Dysregulation of EZH2 contributes to several cancers including lymphomas and prostate cancer. Overexpression of EZH2 results in unchecked cellular proliferation and tumor growth. Moreover chronic obstructive pulmonary disease (COPD) has shown links to this protein where altered expression affects inflammatory responses. Proteins such as BRCA1 in prostate cancer showcase the broader interaction network that EZH2 participates in during disease states. Clinical trials involving inhibitors like GSK126 aim to mitigate the oncogenic activities of this methyltransferase highlighting its relevance in therapeutic development.