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MK-8776 (SCH 900776)

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.

MK-8776 (SCH 900776)化学構造

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
JPY 31500 国内在庫あり
JPY 55500 国内在庫あり
JPY 145500 国内在庫あり
JPY 295500 国内在庫なし(納期7~10日)
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]
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製品安全説明書

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MK-8776 (SCH 900776)関連製品

シグナル伝達経路

Chk Signaling Pathways

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
U2OS Function Assay 1 µM 24 h abrogates of cell cycle arrest  22510560
HCT116 Function Assay 1 µM 24 h abrogates of cell cycle arrest  22510560
ML-1 Apoptosis Assay 25/50/100 nM 24 h enhances cytarabine-induced apoptosis 22869869
HL-60 Apoptosis Assay 30/100/300 nM 24 h enhances cytarabine-induced apoptosis 22869869
U937 Function Assay 100-500 nM 4 h  induces increased phosphorylation of H2AX 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  decreases the cytarabine-induced Chk1 autophosphorylation at Ser296 and prevents Cdc25A downregulation 22869869
U2OS  Growth Inhibition Assay 0-10 µM 24/48 h inhibits cell growth dose dependently 22937147
HMEC 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
Su.86.86 Cell Viability Assay 500 nM 72 h results in G1/S-phase accumulation combined with MK-1775 23148684
H2009 Cell Viability Assay 500 nM 72 h results in G1/S-phase accumulation combined with MK-1775 23148684
HCC2998 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
U20S Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
A498 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
TK10 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
AsPC-1 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
H23 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
H1993 Growth Inhibition Assay 500 nM 24 h enhances the chemosensitization to PMX 24113549
H1299 Growth Inhibition Assay 500 nM 24 h enhances the chemosensitization to PMX 24113549
MiaPaCa-2 Growth Inhibition Assay 10-1000 nM 24-48h enhances the chemosensitization to 23804422
BxPC-3 Growth Inhibition Assay 10-1000 nM 24-48h enhances the chemosensitization to 23804422
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
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
MOLM-13  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
MV-4-11 Apoptosis Assay 100-700 nM 48 h induces apoptosis dose dependently 23536721
OVCAR-8 Growth Inhibition Assay 0.3 µM 8 d sensitizes the cell lines to 23548269
U251 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
HCT115 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
SW620 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
IGROV-1 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
HCT116 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
MCF10A Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
MiaPaCa-2 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
MDA-MB-231 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
U87 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
MDA-MB-435 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
SNB19 Growth Inhibition Assay 200/2000 nM 24 h decreases the IC50 of 24359526
AsPC-1 Growth Inhibition Assay 10-1000 nM 24-48h enhances the chemosensitization to 23804422
SKOV3 Growth Inhibition Assay 0.3 µM 8 d sensitizes the cell lines to 23548269
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. 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
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
Western blot Cyclin E / pY15-CDK / γH2AX p-chk1(ser345) / CDC25A 26595527
In Vivo
In Vivo

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 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
NCT00779584 Completed
Hodgkin Disease|Lymphoma Non-Hodgkin|Neoplasms
Merck Sharp & Dohme LLC
 October 17 2008 Phase 1

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

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

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）

mg/kg g μL 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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Handling Instructions

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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.

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