GSK126

別名：GSK2816126A, GSK2816126

製品コード：S7061 純度：99.91%

GSK126 (GSK2816126A、GSK2816126) は強力で選択性の高い EZH2 メチルトランスフェラーゼ (methyltransferase) 阻害剤(IC50=9.9 nM)であり、EZH2 に対して 20 種類以上の他のヒトメチルトランスフェラーゼよりも 1000 倍以上の選択性を持ちます。

CAS No. 1346574-57-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40300	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 71500	国内在庫あり
100mg	JPY 149500	国内在庫あり
1g	JPY 295500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（159）

製品安全説明書

現在のバッチを見る：純度： 99.91%

99.91

GSK126関連製品

関連ターゲット	Menin-MLL interaction WDR5-MLL interaction	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Highly Selective Inhibitor Library	もっと見る

シグナル伝達経路

Histone Methyltransferaseシグナル伝達経路

Histone Methyltransferase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
human U2932 cells	Cytotoxic assay	72 h	Cytotoxicity against human U2932 cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=6.7 μM.	24767850
human PC3 cells	Cytotoxic assay	72 h	Cytotoxicity against human PC3 cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=9.4 μM.	24767850
human Daudi cells	Cytotoxic assay	72 h	Cytotoxicity against human Daudi cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=11.2 μM.	24767850
human T98G cells	Cytotoxic assay	72 h	Cytotoxicity against human T98G cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=12.6 μM.	24767850
human A549 cells	Cytotoxic assay	72 h	Cytotoxicity against human A549 cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=18.7 μM.	24767850
human U87MG cells	Cytotoxic assay	72 h	Cytotoxicity against human U87MG cells assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=28.5 μM.	24767850
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=0.28 μM.	26189078
human Pfeiffer cells	Cytotoxic assay	72 h	Cytotoxicity against human Pfeiffer cells expressing EZH2 A667G mutant assessed as growth inhibition after 72 hrs by WST-1 assay, GI50=0.18 μM.	24767850
infected SF9 cells			Binding affinity to EZH2 (unknown origin) expressed in baculovirus infected SF9 cells co-expressing SUZ12/EED/RbAp48 complex assessed as binding off-rate at 0.4 uM incubated for 20 mins by Q-TOF mass spectrometry	27512831
A673 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
MG 63 (6-TG R) cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
SK-N-MC cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
LAN-5 cells			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
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生物活性

製品説明

Targets

EZH2 ^[1]
(Cell-free assay)

9.9 nM

In Vitro
In vitro	In vitro, GSK126 most potently inhibits H3K27me3, followed by H3K27me2 in both EZH2 wild-type and mutant DLBCL cell lines. GSK126 also effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines, and induces transcriptional activation of EZH2 target genes in sensitive cell lines. ^[1] In A687V EZH2-mutant cells, GSK126 treatment results in a global decrease in H3K27me3, robust gene activation, caspase activation, and decreased proliferation. ^[2] In parental H2087 cells, GSK126 inhibits the expression of VEGF-A and phosphorylated Ser(473)-AKT, and thus causes the inhibition of cell proliferation, migration and metastasis. ^[3]
Kinase Assay	EZH2 assay
Kinase Assay	The five-member PRC2 complex (Flag–EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant EZH2 is prepared. GSK126 is dissolved in DMSO and tested at concentrations of 0.6 nM to 300 nM with a final DMSO concentration of 2.5%. In contrast to wild-type EZH2 which prefers H3K27me0 as a substrate in vitro, EZH2 Y641 mutants prefer H3K27me2 and have little activity with H3K27me0 or H3K27me1. The A677G mutant is distinct from both the wild-type and Y641 mutant forms of EZH2 in that it efficiently methylates H3K27me0, H3K27me1, and H3K27me2; therefore, histone H3 peptides (residues 21–44; 10 μM final) with either K27me0 (wild type, A677G EZH2), K27me1 (A677G EZH2), or K27me2 (A677G, Y641N, Y641C, Y641H, Y641S and Y641F EZH2) are used as methyltransferase substrates. GSK126 is added to plates followed by addition of 6 nM EZH2 complex and peptide. As the potency of GSK126 is at or near the tight binding limit of an assay run at [SAM] = Km, IC50 values are measured at a high concentration of the competitive substrate SAM relative to its Km (7.5 μM SAM where the SAM Km is 0.3 μM). Under these conditions, the contribution from the enzyme concentration becomes relatively small and accurate estimates of Ki can be calculated. Reactions are initiated with [³H]-SAM, incubated for 30 min, quenched with the addition of 500-fold excess unlabelled SAM, and the methylated product peptide is captured on phosphocellulose filters according to the vendor supplied protocol for MSPH Multiscreen plates. Plates are read on a TopCount after adding 20 μL of Microscint-20 cocktail. Apparent Ki values are calculated using the Cheng–Prusoff relationship for a competitive inhibitor. IC50=Ki (1+[S]/Km)+[E]/2, where E is the enzyme and S is the substrate.
細胞実験	細胞株	46 lymphoma cell lines
	濃度	0~10 μM
	反応時間	6 days
	実験の流れ	The optimal cell seeding is determined empirically for all cell lines by examining the growth of a wide range of seeding densities in a 384-well format to identify conditions that permitted proliferation for 6 days. Cells are then plated at the optimal seeding density 24 h before treatment (in duplicate) with a 20-point two fold dilution series of GSK126 or 0.15% DMSO. Plates are incubated for 6 days at 37°C in 5% CO₂. Cells are then lysed with CellTiter-Glo (CTG) and chemiluminescent signal is detected with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values obtained after the 6 day treatment are expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a four-parameter equation to generate a concentration response curve and the concentration of GSK126 required to inhibit 50% of growth (growth IC50) is determined.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	β-catenin / c-Myc / LEF1 / DVL2 / DVL3 / p-GSK3β XIAP / Survivin / MCL-1 / BID / BIM / BAX / BCL-xl/ Bcl-2 H3K27Me3 / EZH2		27926488
	Immunofluorescence	H3K27me3		25053977
	Growth inhibition assay	Cell proliferation Cell viability		29685965

In Vivo
In Vivo	In mice bearing KARPAS-422 and Pfeiffer xenografts, GSK126 (150 mg/kg/d, i.p.) decreases global H3K27me3, increases gene expression, and thus causes marked tumour regression. ^[1]
動物実験	動物モデル	Female beige SCID mice bearing Pfeiffer or KARPAS-422 tumors
	投与量	150 mg/kg/day
	投与経路	i.p.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT02082977	Terminated	Cancer\|Neoplasms	GlaxoSmithKline	April 24 2014	Phase 1

参考
[1] McCabe MT, et al. Nature. 2012, 492(7427), 108-112. [2] Ott HM, et al. Mol Cancer Ther. 2014, 13(12), 3062-3073. [3] Takeshima H, et al. Carcinogenesis. 2015, 36(2), 192-201.

参考

化学情報

分子量	526.67	化学式	C₃₁H₃₈N₆O₂
CAS No.	1346574-57-9	SDF	Download GSK126 SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 5 mg/mL ( (9.49 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 4 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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よくある質問（FAQ）

質問1:
Could you please suggest a vehicle for in vivo uses without oil?

回答
S7061 could be dissolved in 4% DMSO+30% PEG 300+ddH2O (0.5mg/ml).

質問2:
Does this drug require an activation step to be functional? For example, an acidic or basic environment.

回答
GSK126 does not require an activation step to be functional.

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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):