MK-8776 (SCH 900776)

製品コード：S2735 純度：99.98%

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

CAS No. 891494-63-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 31500	国内在庫あり
10mg	JPY 55500	国内在庫あり
50mg	JPY 145500	国内在庫あり
500mg	JPY 295500	国内在庫なし(納期7~10日)
1g	JPY 748500	国内在庫なし(納期7~10日)

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（68）

製品安全説明書

現在のバッチを見る：純度： 99.98%

99.98

MK-8776 (SCH 900776)関連製品

関連ターゲット	Chk1 Chk2	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

Chkシグナル伝達経路

Chk阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SKOV3	Growth Inhibition Assay	0.3 µM	8 d	sensitizes the cell lines to gemcitabine	23548269
BxPC-3	Growth Inhibition Assay	10-1000 nM	24-48h	enhances the chemosensitization to gemcitabine	23804422
MiaPaCa-2	Growth Inhibition Assay	10-1000 nM	24-48h	enhances the chemosensitization to gemcitabine	23804422
AsPC-1	Growth Inhibition Assay	10-1000 nM	24-48h	enhances the chemosensitization to gemcitabine	23804422
H1299	Growth Inhibition Assay	500 nM	24 h	enhances the chemosensitization to PMX	24113549
H1993	Growth Inhibition Assay	500 nM	24 h	enhances the chemosensitization to PMX	24113549
H1437	Growth Inhibition Assay	500 nM	24 h	enhances the chemosensitization to PMX	24113549
H23	Growth Inhibition Assay	500 nM	24 h	enhances the chemosensitization to PMX	24113549
AsPC-1	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
TK10	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
A498	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
U20S	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
SNB19	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
MDA-MB-435	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
U87	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
HCC2998	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
MDA-MB-231	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
MiaPaCa-2	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
MCF10A	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
HCT116	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
IGROV-1	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
SW620	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
HCT115	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
U251	Growth Inhibition Assay	200/2000 nM	24 h	decreases the IC50 of Gemcitabine	24359526
OVCAR-8	Growth Inhibition Assay	0.3 µM	8 d	sensitizes the cell lines to gemcitabine	23548269
MV-4-11	Apoptosis Assay	100-700 nM	48 h	induces apoptosis dose dependently	23536721
U937	Apoptosis Assay	100-700 nM	48 h	induces apoptosis dose dependently	23536721
MOLM-13	Apoptosis Assay	100-700 nM	48 h	induces apoptosis dose dependently	23536721
A2058	Cell Viability Assay	37.5-300 nM	72 h	reduces the MK-1775 EC50 by 5-fold to an average of 45 nM	23148684
H2009	Cell Viability Assay	500 nM	72 h	results in G1/S-phase accumulation combined with MK-1775	23148684
Su.86.86	Cell Viability Assay	500 nM	72 h	results in G1/S-phase accumulation combined with MK-1775	23148684
HRE	Cell Viability Assay	500 nM	72 h	results in G1/S-phase accumulation combined with MK-1775	23148684
HMEC	Cell Viability Assay	500 nM	72 h	results in G1/S-phase accumulation combined with MK-1775	23148684
U2OS	Function Assay	2 µM	0-24 h	induces phosphorylation of Chk1 at serine 345 at both concentrations as early as 2 h after administration	22937147
U2OS	Growth Inhibition Assay	0-10 µM	24/48 h	inhibits cell growth dose dependently	22937147
U937	Function Assay	100-500 nM	4 h	decreases the cytarabine-induced Chk1 autophosphorylation at Ser296 and prevents Cdc25A downregulation	22869869
U937	Function Assay	100 nM	4 h	reverses the cytarabine-induced inhibition of 3H-thymidine incorporation into DNA	22869869
U937	Function Assay	100-500 nM	4 h	induces increased phosphorylation of H2AX	22869869
HL-60	Apoptosis Assay	30/100/300 nM	24 h	enhances cytarabine-induced apoptosis	22869869
ML-1	Apoptosis Assay	25/50/100 nM	24 h	enhances cytarabine-induced apoptosis	22869869
HCT116	Function Assay	1 µM	24 h	abrogates of cell cycle arrest	22510560
U2OS	Function Assay	1 µM	24 h	abrogates of cell cycle arrest	22510560
Sf9	Function assay			Inhibition of recombinant CDK2/Cyclin A expressed in insect Sf9 cells assessed as inhibition of [33P]-ATP incorporation into biotinylated histone H1 after 1 hr by liquid scintillation counting, IC50 = 0.16 μM.	21094607
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生物活性

製品説明

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

Targets

Chk1 ^[1] (Cell-free assay)	CDK2 ^[1] (Cell-free assay)
3 nM	0.16 μM

In Vitro
In vitro	SCH 900776 is a less potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhances the γ-H2AX response of hydroxyurea, 5-fluoruracil, and cytarabine. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.^[1]
Kinase Assay	Chk1 SPA assay
Kinase Assay	An in vitro assay utilizing recombinant His-Chk1 expressed in the baculovirus expression system as an enzyme source and biotinylated peptide based upon CDC25C as substrate. His-Chk1 is diluted to 32 nM in kinase buffer containing 50 mM Tris pH 8.0, 10 mM MgCl₂, and 1 mM DTT. CDC25C (CDC25 Ser216 C-term biotinylated peptide) peptide is diluted to 1.93 μM in kinase buffer. For each kinase reaction, 20 μL of 32 nM Chk1 enzyme solution and 20 μL of 1.926 μM CDC25C are mixed and combined with 10 μL of SCH 900776 diluted in 10% DMSO, making final reaction concentrations of 6.2 nM Chk1, 385 nM CDC25C and 1% DMSO after addition of start solution. The reaction is started by addition of 50 μL of start solution consisting of 2 μM ATP and 0.2 μCi of ³³P-ATP, making a final reaction concentration of 1 μM ATP, with 0.2 μCi of ³³P-ATP per reaction. Kinase reactions run for 2 hours at room temperature and are stopped by the addition of 100 μL of stop solution consisting of 2 M NaCl, 1% H₃PO₄, and 5 mg/mL Streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl with 1% phosphoric acid. Signal is then assayed using a TopCount 96-well liquid scintillation counter. Dose-response curves are generated from duplicate 8 point serial dilutions of SCH 900776. IC50 values are derived by nonlinear regression analysis.
細胞実験	細胞株	mESCs
	濃度	10 μM
	反応時間	1 h
	実験の流れ	Cells were treated with inhibitors or vehicle for 1 hour
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	Cyclin E / pY15-CDK / γH2AX p-chk1(ser345) / CDC25A		26595527

In Vivo
In Vivo	Administered 30 minutes after gemcitabine, 4 mg/kg SCH 900776 is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice. ^[1]
動物実験	動物モデル	Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
	投与量	~50 mg/kg
	投与経路	Administered intraperitoneally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT00779584	Completed	Hodgkin Disease\|Lymphoma Non-Hodgkin\|Neoplasms	Merck Sharp & Dohme LLC	October 17 2008	Phase 1

参考
[1] Guzi TJ, et al. Mol Cancer Ther, 2011, 10(4), 591-602. [2] Montano R, et al. Mol Cancer Ther, 2012, 11(2), 427-438. [3] Schenk EL, et al. Clin Cancer Res, 2012, 18(19), 5364-5373. [4] Grow EJ, et al. Nat Genet. 2021 Aug;53(8):1207-1220. + 展開

参考

[4] Grow EJ, et al. Nat Genet. 2021 Aug;53(8):1207-1220.

+ 展開

化学情報

分子量	376.25	化学式	C₁₅H₁₈BrN₇
CAS No.	891494-63-6	SDF	Download MK-8776 (SCH 900776) SDFをダウンロードする
Smiles	CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)C4CCCNC4
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 : 75 mg/mL ( (199.33 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。)

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。

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Handling Instructions

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* 必須

よくある質問（FAQ）

質問1:
I would like to know whether your product S2735 is the optically pure R enantiomer or whether it is a racemic mix.

回答
Our S2735 MK-8776 (SCH 900776) is R enantiomer.

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):