SCH900776(R)
MK-8776 (SCH 900776)
CAS: 891494-63-6
Molecular Formula: C15H18BrN7
SCH900776(R) - Names and Identifiers
SCH900776(R) - Physico-chemical Properties
| Molecular Formula | C15H18BrN7 |
| Molar Mass | 376.25 |
| Density | 1.80 |
| Solubility | Soluble in DMSO, not in water |
| pKa | 8.88±0.10(Predicted) |
| Storage Condition | -20℃ |
| Use | SCH900776 (MK-8776) is an effective, selective, orally available Chk1 inhibitor with an IC50 value of 3 nM; it is 50 and 500 times more selective than CDK2 and Chk2, respectively. |
| In vitro study | SCH 900776 is not a 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 Industry Chk1 pS345 following exposure to SCH 900776 as part of a fuel cycle, perhaps driven by AT-family possibilities and DNA-PK. SCH 900776 is an inefficient inhibitor of Chk2 and CDK2 with an IC50 of 1.5 μm and 0.16 μm, respectively. SCH 900776 had no significant inhibitory effect on cytochrome P450 human liver microsomal subtypes 1A2,2C9,2C19,2D6, and 3A4. After 24 hours of hydroxyurea exposure, SCH 900776 induced a dose-dependent loss of DNA replication capacity. SCH 900776 enhances the response of γ-H2AX to hydroxyurea, 5-fluorouracil, and arabinoside. In combination with the antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicating disruption of the replication fork, and double-stranded DNA breaks. In addition, SCH 900776 inhibited the accumulation of Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776, associated with rapid, dose-dependent aggregation of Chk1 pS345, suggests that a circulating population of normal cells induces Chk1 pS345 exposure to SCH After 900776, there is a portion of the null cycle, which may be driven by AT-family kinases and DNA-PK. |
| In vivo study | 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 Orders of SCH 900776. 4 mg/kg SCH 900776 is sufficient to induce γ-H2AX biomarkers 30 minutes after administration of gemcitabine relative to Gemcitabine or SCH 900776 alone, and 8 mg/kg enhanced tumor pharmacodynamics and regression response. Increasing doses of SCH 900776 (16 mg/kg and 32 mg/kg) induced continuous improvement in tumor response. Importantly, in BALB/c mice, the dose of SCH 900776 was associated with strong biomarker activation, while the increased tumor response was not associated with increased toxicity of gemcitabine to hematologic markers. |
SCH900776(R) - Reference
| Reference Show more | 1: Sakurikar N, Eastman A. Will targeting Chk1 have a role in the future of cancer therapy? J Clin Oncol. 2015 Mar 20;33(9):1075-7. doi: 10.1200/JCO.2014.60.0767. Epub 2015 Feb 17. PubMed PMID: 25691674. 2: Daud AI, Ashworth MT, Strosberg J, Goldman JW, Mendelson D, Springett G, Venook AP, Loechner S, Rosen LS, Shanahan F, Parry D, Shumway S, Grabowsky JA, Freshwater T, Sorge C, Kang SP, Isaacs R, Munster PN. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors. J Clin Oncol. 2015 Mar 20;33(9):1060-6. doi: 10.1200/JCO.2014.57.5027. Epub 2015 Jan 20. PubMed PMID: 25605849. 3: Lv M, Ma S, Tian Y, Zhang X, Lv W, Zhai H. Computational studies on the binding mechanism between triazolone inhibitors and Chk1 by molecular docking and molecular dynamics. Mol Biosyst. 2015 Jan;11(1):275-86. doi: 10.1039/c4mb00449c. Epub 2014 Nov 5. PubMed PMID: 25372494. |
SCH900776(R) - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.658 ml | 13.289 ml | 26.578 ml |
| 5 mM | 0.532 ml | 2.658 ml | 5.316 ml |
| 10 mM | 0.266 ml | 1.329 ml | 2.658 ml |
| 5 mM | 0.053 ml | 0.266 ml | 0.532 ml |
Last Update：2024-01-02 23:10:35
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Product Name: MK-8776 (SCH 900776) Visit Supplier Webpage Request for quotation
CAS: 891494-63-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 891494-63-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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