연구용

EPZ-6438 (Tazemetostat) EZH2 inhibitor

제품 번호S7128

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.

EPZ-6438 (Tazemetostat) EZH2 inhibitor Chemical Structure

화학 구조

분자량: 572.74

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품질 관리 (Quality Control)

배치: 순도: 99.90%

99.90

함께 자주 사용되는 제품 EPZ-6438 (Tazemetostat)

This compound and UNC1999 treatment reduce liver steatosis in STAM non-alcoholic steatohepatitis (NASH) mice.

Lirametostat (CPI-1205)

This compound and Lirametostat are small-molecule EZH2 inhibitors that exhibit antineoplastic effects in hematologic malignancies.

Valemetostat (DS-3201)

This compound and Valemetostat are EZH2 inhibitors that induce proliferation arrest, differentiation, and apoptosis in diffuse large B-cell lymphoma (DLBCL) cells.

관련 타겟	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT AMPK Histone Acetyltransferase
기타 EZH2 억제제	PF-06821497 GSK126 Tulmimetostat (CPI-0209) GSK343 CPI-169 MS1943 EBI-2511 EZH2/HSP90-IN-29 SHR2554

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주	분석 유형	농도	배양 시간	제형	활성 설명	PMID
human HeLa cells	Function assay		72 h		Inhibition of EZH2 in human HeLa cells assessed as reduction in H3K27me3 levels incubated for 72 hrs by ELISA method, IC50=0.02 μM.	26189078
Sf9	Function assay		2 h		Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fl, IC50 = 0.004 μM.	29456795
KARPAS422	Antiproliferative activity assay		3 to 4 days up to 14 days		Antiproliferative activity against human KARPAS422 cells harboring monoallelic Y641N EZH2 mutation assessed as reduction in cell viability measured every 3 to 4 days up to 14 days by Beckman Coulter-based method, IC50 = 0.012 μM.	28092155
Pfeiffer	Cytotoxicity assay		5 days		Cytotoxicity against human Pfeiffer cells assessed as decrease in cell viability after 5 days by CellTiter-Glo reagent based luminescence assay, IC50 = 0.038 μM.	29456795
G401	Function assay		48 h		Inhibition of EED in human G401 cells assessed as reduction in global H3K27me3 level after 48 hrs by ELISA, IC50 = 0.04 μM.	28092155
G401	Function assay		4 h		Inhibition of methyltransferase activity of EZH2 in human G401 cells assessed as H3K27 trimethylation after 4 hrs by ELISA, EC50 = 0.2 μM.	26769278
Pfeiffer	Antitumor assay	100 mg/kg	20 days		Antitumor activity against human Pfeiffer cells xenografted in athymic nude mouse assessed as tumor growth inhibition at 100 mg/kg, po qd administered for 20 days measured twice per week	29456795
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량	572.74	화학식	C₃₄H₄₄N₄O₄	보관 (수령일로부터)	3년-20°C분말
CAS 번호	1403254-99-8	SDF 다운로드		원액 보관	1년-80°C용매에 보관 1개월-20°C용매에 보관
동의어	E7438			Smiles	CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (174.59 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (174.59 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (174.59 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (174.59 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (174.59 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량	농도	부피	분자량
=	×	×

희석 계산기 분자량 계산기

In vivo 배치:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Selleck 연구소에서 검증되었습니다. 이 제형에 대한 조정이 필요한 경우 맞춤 테스트를 위해 당사 영업팀에 문의하십시오.	0.630mg/ml (1.10mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

투여량: mg/kg 동물 평균 체중: g 동물당 투여량:μL 동물 수:

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH₂O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

특징	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.
Targets/IC₅₀/Ki	EZH2 (Cell-free assay) 2.5 nM(Ki)
시험관 내(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. The antiproliferative effect of this compound is enhanced by either NSC-9900 or Hexadecadrol in several EZH2 mutant lymphoma cell lines.
키나아제 분석	Biochemical Methods
키나아제 분석	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.
생체 내(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.
참조	[1] https://pubmed.ncbi.nlm.nih.gov/23620515/ [2] https://ash.confex.com/ash/2013/webprogram/Paper61408.html

적용 분야 (Applications)

방법	바이오마커	이미지	PMID
Western blot	EZH2 H3K27me3		26360609
Immunofluorescence	HP1/Rap1		29670078

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Could you please help test the formulation of it for in vivo studies?

답변:
We've tried some vehicles for it, and found this compound can be dissolved in 2% DMSO+30% PEG 300+5% Tween+ddH2O at 5 mg/ml as a clear solution. Dissolved in 5% DMSO+0.5% CMC Na at 15 mg/ml, it is a suspension for oral gavage.

product.CellLines}	product.AssayType}	product.Concentration}	product.IncubationTime}	product.Formulation}	product.ActivityDescription}	PMID

희석 계산기

스톡 솔루션 준비에 필요한 희석을 계산하십시오. Selleck 희석 계산기는 다음 방정식을 기반으로 합니다.

농도 _(시작) x 볼륨 _(시작) = 농도 _(최종) x 볼륨 _(최종)

이 방정식은 일반적으로 다음과 같이 약칭됩니다. C1V1 = C2V2 ( 입력 출력 )

*스톡 용액을 준비할 때는 항상 바이알 라벨 및 MSDS / COA (온라인에서 사용 가능)에 있는 제품의 배치별 분자량을 사용하십시오.

연속 희석 계산기 방정식

연속 희석

농도 (시작):

희석 배율:

계산된 결과

C1=C0/X	C1:		LOG(C1):
C2=C1/X	C2:		LOG(C2):
C3=C2/X	C3:		LOG(C3):
C4=C3/X	C4:		LOG(C4):
C5=C4/X	C5:		LOG(C5):
C6=C5/X	C6:		LOG(C6):
C7=C6/X	C7:		LOG(C7):
C8=C7/X	C8:		LOG(C8):