SCH772984

製品コード：S7101 純度：99.99%

SCH772984 is a novel, specific inhibitor of ERK1/2 with IC50 values of 4 nM and 1 nM in cell-free assay, respectively, And show robust efficacy in RAS- or BRAF-mutant cancer cells.

CAS No. 942183-80-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 50500	国内在庫なし(納期7~10日)
1mg	JPY 22000	国内在庫あり
5mg	JPY 40500	国内在庫あり
25mg	JPY 88500	国内在庫あり
100mg	JPY 223500	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（503）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

SCH772984と併用されることが多い化合物

Adezmapimod (SB203580)

LY294002 and SCH772984 inhibit the VE-induced granulosa cell proliferation and promoted apoptosis, whereas the SB203580 had the opposite effects.

SP600125

SCH772984 and SP600125 suppress the upregulated LAGE3-induced proliferation, migration, and invasion of Hep3B cells.

Xing Y, et al. Cell Mol Biol Lett. 2021 Nov 27;26(1):49.

MG132

SCH772984-induced downregulation of UHRF1 and DNMT1 proteins is not rescued by MG132 in HCT116 cells.

Li J, et al. Sci Rep. 2019 Jan 29;9(1):907.

Neratinib

SCH772984 decreases the viability of stem-like colon cancer cell lines SW-480 and works synergistically with Neratinib.

Pal R, et al. Cancer Res (2017) 77 (13_Supplement): 5167.

Phenformin HCl

Phenformin enhances the antiproliferative activity of SCH772984 in Mewo, M308, and SK-Mel-113 cells.

Trousil S, et al. J Invest Dermatol. 2017 May; 137(5): 1135–1143.

SCH772984関連製品

関連ターゲット	ERK1 ERK2 ERK5 ERK1/2	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library Anti-alzheimer Disease Compound Library	もっと見る

シグナル伝達経路

ERKシグナル伝達経路

ERK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
A375	Antiproliferative assay	72 hrs	Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant after 72 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.07 μM.	25977981
HT-29	Antiproliferative assay	4 days	Antiproliferative activity against human HT-29 cells harboring BRAF V600E/D mutant measured after 4 days, IC50 = 0.059 μM.	30034615
A375	Function assay	2 hrs	Inhibition of ERK1/2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-RSK level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.02 μM.	25977981
A375	Function assay	2 hrs	Inhibition of ERK1/2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-RSK level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.02 μM.	25977981
COLO205	Antiproliferative assay	4 days	Antiproliferative activity against human COLO205 cells harboring BRAF V600E/D mutant measured after 4 days, IC50 = 0.016 μM.	30034615
A375	Function assay	2 hrs	Inhibition of ERK2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-ERK2 level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.004 μM.	25977981
HT-29	Apoptosis assay		Induction of apoptosis in human HT-29 cells harboring BRAF/KRAS mutant by caspase activation assay, IC50 = 0.096 μM.	29748051
HT-29	Antiproliferative assay		Antiproliferative activity against human HT-29 cells harboring BRAF/KRAS mutant, IC50 = 0.059 μM.	29748051
A375	Function assay		Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated RSK levels, IC50 = 0.02 μM.	28376306
A375	Function assay		Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated ERK2 levels, IC50 = 0.004 μM.	28376306
2P-ERK2	Growth Inhibition Assay		IC50=0.24 nM	25350931
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生物活性

製品説明

SCH772984 is a novel, specific inhibitor of ERK1/2 with IC50 values of 4 nM and 1 nM in cell-free assay, respectively, And show robust efficacy in RAS- or BRAF-mutant cancer cells.

特性

Does not directly inhibit MEK1, MEK2, BRAF, or CRAF enzyme activity.

Targets

ERK2 ^[1] (Cell-free assay)	ERK1 ^[1] (Cell-free assay)
1 nM	4 nM

In Vitro
In vitro	SCH772984 is a novel, selective and ATP competitive inhibitor of ERK1/2. SCH772984 inhibits phosphorylation of the ERK substrate p90 ribosomal S6 kinase (T359/S363 phospho-RSK) in a dose-dependent manner. SCH772984 also inhibits phosphorylation of residues in the activation loop of ERK itself. SCH772984 demonstrates EC50 values <500 nM in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. ^[1]
Kinase Assay	ERK2 IMAP enzymatic assay
Kinase Assay	SCH772984 is tested in 8 point dilution curves in duplicate against purified ERK2 or ERK1. The enzyme is added to the reaction plate. and incubated with the compound before adding a solution of substrate peptide and ATP. 14μl of diluted enzyme (0.3ng active ERK2 per reaction) is added to each well of a 384-well plate. The plates are gently shaken to mix the reagents and incubated for 45 minutes at room temperature. The reaction is stopped with 60μl of IMAP Binding Solution (1:2200 dilutions of IMAP beads in 1X Binding Buffer). The plates are incubated at room temperature for an additional 0.5 hours to allow complete binding of phosphopeptides to the IMAP beads. Plates are read on the LJL Analyst.
細胞実験	細胞株	BRAF-mutant or RAS-mutant tumor lines
	濃度	~10 μM
	反応時間	5 days
	実験の流れ	Cell proliferation experiments are performed in a 96-well format (six replicates), and cells are plated at 4,000/well density. At 24 h after cell seeding, cells are treated with DMSO or 9 point IC50 dilution (0.001-10 μM) at 1% DMSO final for all concentrations. Viability is assayed on 5 days after dosing using ViaLight luminescence kit following the manufacturer’s recommendations. For cell line panel viability assay, cells are treated with SCH772984 for 4 days and assayed by CellTiterGlo luminescent cell viability assay.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	cyclin B1 / cyclin D1 / p21 pRSK / pERK / pAKT / pMEK DUSP1 / DUSP4 / DUSP6 pCRAF(S338, S289, S296, S301) Aurora B / ETS1 / ETS2		26725216
	Growth inhibition assay	Cell viability		30118499
	Immunofluorescence	TOMM20 pERK1/2		30833752

In Vivo
In Vivo	SCH772984 induces tumor regressions in xenograft models at tolerated doses. SCH772984 effectively inhibites MAPK signaling and cell proliferation in BRAF or MEK inhibitor resistant models. ^[1]
動物実験	動物モデル	Nude mice
	投与量	12.5 mg/kg, 25 mg/kg, 50 mg/kg
	投与経路	i.p.

参考
[1] Morris EJ, et al. Cancer Discov, 2013 Apr 29.

参考

[1] Morris EJ, et al. Cancer Discov, 2013 Apr 29.

化学情報

分子量	587.67	化学式	C₃₃H₃₃N₉O₂
CAS No.	942183-80-4	SDF	Download SCH772984 SDFをダウンロードする
Smiles	C1CN(CC1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7
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个月-20°Cin solvent

In vitro
Batch:

DMSO : 14 mg/mL ( (23.82 mM)； Warmed with 50℃ water bath; 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。)

Water : Insoluble

Ethanol : 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

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問1:
I would like to inhibit Erk1/2 by treating the mice with the inhibitor. by what kind of administration way and at what concentration could it be done?

回答
SCH772984 can be administrated by I.P. The dosages can be used as: 12.5 mg/kg, 25 mg/kg, 50 mg/kg. For more detail information please find the paper below: http://cancerdiscovery.aacrjournals.org/content/3/7/742.full

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