MK-8776 (SCH 900776)
MK-8776 (SCH 900776)是一种选择性Chk1抑制剂，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。Phase 2。
MK-8776 (SCH 900776) Chemical Structure
CAS: 891494-63-6
客户使用Selleck的MK-8776 (SCH 900776)发表文献68篇
产品质控
MK-8776 (SCH 900776)相关产品
| 相关靶点 | Chk1 Chk2 | 点击展开 |
|---|---|---|
| 相关化合物库 | 激酶抑制剂库 PI3K/Akt 抑制剂库 MAPK抑制剂库 DNA损伤/ DNA修复化合物库 细胞周期化合物库 | 点击展开 |
相关信号通路图
Chk抑制剂选择性比较
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| 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 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | MK-8776 (SCH 900776)是一种选择性Chk1抑制剂，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。Phase 2。 | ||||
|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | SCH 900776是Chk2和CDK2的低效抑制剂，IC50分别为1.5 μM 和 0.16 μM。SCH 900776对细胞色素P450人肝微粒体亚型1A2，2C9，2C19，2D6，和3A4没有显著的抑制作用。羟基脲下暴露24小时后，SCH 900776诱导DNA复制能力剂量依赖性损失。SCH 900776增强γ-H2AX对羟基脲，5-氟尿嘧啶，和阿糖孢苷的响应。与抗代谢物结合，SCH 900776在2小时内诱导γ-H2AX的累积，表明复制叉瓦解，并且双链DNA断裂。此外，SCH 900776以剂量依赖的方式抑制Chk1 pS296自磷酸化的积累。增殖的WS1细胞暴露于SCH 900776，与Chk1 pS345快速的，剂量依赖性聚集相关，表明正常细胞的循环群诱导Chk1 pS345在暴露于SCH 900776后，是一部分无效循环，这也许通过AT-家族激酶和DNA-PK驱动。[1] |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | Cyclin E / pY15-CDK / γH2AX p-chk1(ser345) / CDC25A |
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26595527 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 |
相对于gemcitabine或SCH 900776单独给药，Gemcitabine给药30分钟后，4 mg/kg SCH 900776足以诱导γ-H2AX生物标志物，而8 mg/kg增强肿瘤药效动力学和退化响应。递增剂量的SCH 900776 (16 mg/kg和32 mg/kg)诱导肿瘤响应持续改进。重要的是，在BALB/c 小鼠体内，SCH 900776的剂量与强的生物标志物活化相关，而提高的肿瘤响应与gemcitabine对血液学指标增强的毒性无关。[1] |
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|---|---|---|
| 动物实验 | Animal Models | 皮下注射A2780 或 MiaPaCa2细胞的额雌性裸鼠 |
| Dosages | ~50 mg/kg | |
| Administration | 腹腔内注射 | |
| 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 |
化学信息&溶解度
| 分子量 | 376.25 | 分子式 | C15H18BrN7 |
| CAS号 | 891494-63-6 | SDF | Download MK-8776 (SCH 900776) SDF |
| Smiles | CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)C4CCCNC4 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 75 mg/mL ( (199.33 mM)； DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 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.
