Tazemetostat (EPZ-6438)

製品コードS7128 バッチS712819

化学情報

	Synonyms	E7438	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₃₄H₄₄N₄O₄
	分子量	572.74	CAS No.	1403254-99-8
Solubility (25°C)*	体外	DMSO	100 mg/mL (174.59 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with K_i and IC50 of 2.5 nM and 11 nM in cell-free assays, exhibiting a 35-fold selectivity versus EZH1 and >4,500-fold selectivity relative to 14 other HMTs.
in vitro	Tazemetostat (EPZ-6438) concentration-dependently reduces global H3K27Me3 levels in wild-type or SMARCB1 mutant cells, and induces strong antiproliferative effects with IC50 ranging from 32 nM to 1000 nM in SMARCB1-deleted MRT cell lines. It induces gene expression of neuronal differentiation and cell cycle inhibition, while inhibtis expression of Hedgehog pathway genes, MYC and EZH2. ^[1] The antiproliferative effect of this compound is enhanced by either NSC-9900 or Hexadecadrol in several EZH2 mutant lymphoma cell lines. ^[2]
in vivo	In SCID mice bearing s.c. G401 xenografts, Tazemetostat (EPZ-6438) induces tumor stasis during the administration period and produces a significant tumor growth delay with minimal effect on body weight. ^[1]
特徴	Orally bioavailable EZH2-selective inhibitor for both wild-type and mutant. Currently being tested in Phase II clinical trials for treatment of Diffuse Large B Cell Lymphoma.

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical Methods
キナーゼアッセイ	Tazemetostat (EPZ-6438) is incubated for 30 min with 40 μL per well of 5 nM PRC2 (final assay concentration in 50 μL is 4 nM ) in 1X assay buffer (20 mM Bicine [pH 7.6], 0.002% Tween-20, 0.005% Bovine Skin Gelatin and 0.5 mM DTT). 10 μL per well of substrate mix comprising assay buffer 3 H-SAM, unlabeled SAM, and peptide representing histone H3 residues 21-44 containing C-terminal biotin (appended to a C-terminal amide-capped lysine) are added to initiate the reaction (both substrates are present in the final reaction mixture at their respective Km values, an assay format referred to as ‘‘balanced conditions’’. The final concentrations of substrates and methylation state of the substrate peptide are indicated for each enzyme Reactions are incubated for 90 min at room temperature and quenched with 10 μL per well of 600 μM unlabeled SAM, Then transferred to a 384-well flashplate and washed after 30 min.
細胞アッセイ	細胞株	Mutant cell lines (G401, A204, G402, KYM-1), Wild type cell line (RD, 293, SJCRH30)
	濃度	~10 μM
	反応時間	7 days
	実験の流れ	For the adherent cell line proliferation assays, plating densities for each cell line are determined based on growth curves (measured by ATP content) and density over a 7-d time course. On the day before compound treatment, cells are plated in either 96-well plates in triplicate (for the day 0–7 time course) or 6-well plates (for replating on day 7 for the remainder of the time course). On day 0, cells are either untreated, DMSO-treated, or treated with Tazemetostat (EPZ-6438) starting at 10 µM and decreasing in either threefold or fourfold dilutions. Plates are read on day 0, day 4, and day 7 using Cell Titer Glo, with compound/media being replenished on day 4. On day 7, the six-well plates are trypsinized, centrifuged, and resuspended in fresh media for counting by Vi-Cell. Cells from each treatment are replated at the original density in 96-well plates in triplicate. Cells are allowed to adhere to the plate overnight, and cells are treated as on day 0. On days 7, 11, and 14, plates are read using Cell Titer Glo, with compound/media being replenished on day 11. Averages of triplicates are used to plot proliferation over the time course, and calculate IC50 values. For cell cycle and apoptosis, G401 and RD cells are plated in 15-cm dishes in duplicate at a density of 1 × 10⁶ cells per plate. Cells are incubated with this compound at 1 µM, in a total of 25 mL, over a course of 14 d, with cells being split back to original plating density on day 4, 7, and 11. Cell cycle analysis and TUNEL assay are performed using a Guava flow cytometer, following the manufacturer’s protocol.
動物実験	動物モデル	SCID mice bearing s.c. G401 xenografts.
	投薬量	~500 mg/kg
	投与方法	Oral administration

参考

https://pubmed.ncbi.nlm.nih.gov/23620515/
https://ash.confex.com/ash/2013/webprogram/Paper61408.html

カスタマーフィードバック

: Data from [Data independently produced by , , Cell, 2018, 175(1):186-199]

: Data from [Data independently produced by , , J Pathol, 2017, 242(3):371-383]

: Data from [Data independently produced by , , Clin Epigenetics, 2018, 10(1):121]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer [ Nat Cancer, 2025, 10.1038/s43018-025-00960-z]	PubMed: 40301653
Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing [ Nat Cell Biol, 2025, 27(9):1411-1421]	PubMed: 40897805
Constitutive expression of the transcriptional co-activator IκBζ promotes melanoma growth and immunotherapy resistance [ Nat Commun, 2025, 16(1):5387]	PubMed: 40562773
Single cell suppression profiling of human regulatory T cells [ Nat Commun, 2025, 16(1):1325]	PubMed: 39900891
A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma [ Mol Cell, 2025, 85(11):2110-2127.e7]	PubMed: 40403727
HIF-independent oxygen sensing via KDM6A regulates ferroptosis [ Mol Cell, 2025, 85(15):2973-2987.e6]	PubMed: 40712585
The NEXT complex regulates H3K27me3 levels to affect cancer progression by degrading G4/U-rich lncRNAs [ Nucleic Acids Res, 2025, 53(4)gkaf107]	PubMed: 39988317
Differential regulation of FADS2 by EZH2 reveals a metabolic vulnerability in ovarian cancer treatment [ EBioMedicine, 2025, 119:105879]	PubMed: 40818202
EZH2 inhibition mitigates HIV immune evasion, reduces reservoir formation, and promotes skewing of CD8+ T cells toward less-exhausted phenotypes [ Cell Rep, 2025, 44(5):115652]	PubMed: 40333189
EZH2 inhibition sensitizes MYC-high medulloblastoma cancers to PARP inhibition by regulating NUPR1-mediated DNA repair [ Oncogene, 2025, 44(6):391-405]	PubMed: 39562655

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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