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MK-8776(SCH 900776)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MK-8776(SCH 900776)图片
CAS NO:891494-63-6
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)376.25
FormulaC15H18BrN7
CAS No.891494-63-6
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 3 mg/mL (8.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)4% DMSO+30% Propylene glycol: 5 mg/mL
SynonymsSCH900776; MK8776; SCH-900776; MK-8776; SCH 900776; MK 8776
实验参考方法
In Vitro

In vitro activity: 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.


Kinase Assay: The Kinase Profiler service is used to generate general selectivity data for SCH 900776 against a broad range of serine/threonine and tyrosine kinases. Assays are typically run at two concentrations of SCH 900776 (0.5 and 5 μM), at a fixed (10 μM) concentration of ATP.


Cell Assay: In vitro, SCH 900776 blocked accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Treatment of proliferating WS1 cells with SCH 900776 was found to be associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 in response to the inhibition of SCH 900776 as part of a futile cycle 1.

In VivoAdministered 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.
Animal modelFemale nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
Formulation & DosageFormulated in 20% hydroxypropyl β-cyclodextrin; 50 mg/kg; i.p. injection
ReferencesMol Cancer Ther. 2011 Apr;10(4):591-602.