Home Epigenetics DNA/RNA Synthesis inhibitor EED226

연구용

EED226 DNA/RNA Synthesis inhibitor

제품 번호S8496

EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED.
EED226 DNA/RNA Synthesis inhibitor Chemical Structure

화학 구조

분자량: 369.40

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품질 관리 (Quality Control)

배치: S849601 DMSO]73 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false 순도: 99.93%
99.93

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
KARPAS422 Antiproliferative assay 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 = 0.08 μM. 28092155
G401 Function assay 48 hrs Inhibition of EED in human G401 cells assessed as reduction in global H3K27me3 level after 48 hrs by ELISA, IC50 = 0.22 μM. 28092155
KARPAS422 Antitumor assay 300 mg/kg 34 days Antitumor activity against human KARPAS422 cells xenografted in Balb/C nude mouse assessed as tumor regression at 300 mg/kg, po BID for 34 days 28092155
KARPAS422 Antitumor assay 1.5 to 40 mg/kg 2 weeks Antitumor activity against human KARPAS422 cells xenografted in Balb/C nude mouse assessed as reduction in tumor volume at 1.5 to 40 mg/kg, po BID for 2 weeks 28092155
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 369.40 화학식

C17H15N5O3S

 보관 (수령일로부터)
CAS 번호 2083627-02-3 SDF 다운로드 원액 보관

동의어 N/A Smiles CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(N3C2=NN=C3)NCC4=CC=CO4

용해도 (Solubility)

In vitro
배치:

DMSO : 73 mg/mL (197.61 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:

생체 내 제형 계산기 (투명한 용액)

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

mg/kg g μL

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)

Targets/IC50/Ki
EED
82 nM(Kd)
PRC2
114 nM(Kd)
시험관 내(In vitro)
EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. This compound also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. It regulates histone H3K27 methylation and PRC2 target gene expression in cells. In the in vitro enzymatic assays, this chemical inhibits PRC2 with an IC50 (half-maximal inhibitory concentration) of 23.4 nM when the H3K27me0 peptide is used as substrate and an IC50 of 53.5 nM when the mononucleosome is used as the substrate, with the stimulatory H3K27me3 added at 1 × Kact (1.0 μM). It is noncompetitive with both SAM and peptide substrate. This compound bound to EED and PRC2 complex with a 1:1 stoichiometry and Kd of 82 nM and 114 nM, respectively. It does not disrupt the PRC2 complex and could still occupy its binding pocket with a SAM-competitive EZH2 inhibitor bound to PRC2. This chemical shows remarkable selectivity for PRC2 complex over 21 other protein methyltransferases, kinases and other protein classes, The only other histone methyltransferase that can be inhibited by it is the EZH1-PRC2 complex. It with moderate permeability leads to a dose-dependent decrease of both global H3K27me3 and H3K27me2 markers in G401 cell.
생체 내(In vivo)
This compound effectively induces tumor regression in a mouse xenograft model. It in a solid dispersion formulation are well tolerated in animals. This chemical clearly demonstrates a dose-dependent efficacy in the mouse xenograph study. It inhibits the growth of diffuse large B-cell lymphoma (DLBCL) xenografts and reduces H3K27me3 levels to a similar extent as an EZH2 inhibitor. It has very low in vivo and in vitro clearance and approximately 100% oral bioavailability, low volume of distribution (0.8 L/kg), reasonable terminal t1/2 (2.2 h), and moderate plasma protein binding (PPB)(14.4%). Its solubility is relatively low and with little dependency on the pH of the medium.
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