3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide
AZD7762
CAS: 860352-01-8
Molecular Formula: C17H19FN4O2S
3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide - Names and Identifiers
3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide - Physico-chemical Properties
| Molecular Formula | C17H19FN4O2S |
| Molar Mass | 362.42 |
| Density | 1.38 |
| Boling Point | 547.6±50.0 °C(Predicted) |
| Solubility | Soluble in DMSO |
| Appearance | solid |
| Color | Yellow or brown |
| pKa | 9.06±0.20(Predicted) |
| Storage Condition | -20° |
| Stability | Stable for 1 year as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. |
| Use | AZD-7762 is a synthetic small molecule inhibitor of checkpoint kinases (Chks) with potential chemosensitizing activity. AZD7762 binds to and inhibits Chks, which may prevent cell cycle arrest and subsequent nucleotide excision repair in DNA-damaged tumor cells, resulting in tumor cell apoptosis. This agent may enhance the cytotoxicity of DNA-damaging agents. Chks are protein kinases that regulate either G1/S or G2/M transitions in the cell cycle. In the presence of DNA damage or incomplete DNA replication, Chks become activated and initiate cell cycle arrest to allow DNA repair or the completion of DNA replication. |
| In vitro study | AZD7762 is a Chk1 selective inhibitor that inhibits Chk1 phosphorylation of the cdc25C peptide by reversibly binding to the ATP binding site of Chk1 with an IC50 of 5 nM and a Ki of 3.6 nM. AZD7762 induces cell cycle arrest with an EC50 of 0.620 μm, and by blocking cdc25A dependent chk1 degradation and Cyclin A activation, the Camptothecin-induced G2 phase arrest is significantly abolished with an EC50 of 10 nM. 300 nM AZD7762 enhances the anticancer activity of gemcitrate on SW620 and also enhances the anticancer activity of Topotecan on MDA-MB-231 by reducing the GI50 value, from 24.1 nM and 2.25 μm to 1.08 nM and 0.15 μM, respectively. AZD7762 acts on a variety of neuroblastoma cell lines carrying p53 wild-type, p53 mutant, MDM2 addition, or p14 deletion with an IC50 of 82.6 nM to 505.9 nM. AZD7762 is a selective Chk1 inhibitor, Inhibition of Chk1 phosphorylation of the cdc25C peptide by reversible binding to the ATP binding site of Chk1 with an IC50 of 5 nM and a K I of 3.6 nM. AZD7762 induces cell cycle arrest with an EC50 of 0.620 μm, and by blocking cdc25A dependent chk1 degradation and Cyclin A activation, the Camptothecin-induced G2 phase arrest is significantly abolished with an EC50 of 10 nM. 300 nM AZD7762 enhances the anticancer activity of gemcitrate on SW620 and also enhances the anticancer activity of Topotecan on MDA-MB-231 by reducing the GI50 value, from 24.1 nM and 2.25 μm to 1.08 nM and 0.15 μM, respectively. AZD7762 acts on a variety of neuroblastoma cell lines carrying p53 wild-type, p53 mutant, MDM2 addition, or p14 deletion with an IC50 of 82.6 nM to 505.9 nM. |
| In vivo study | AZD7762 alone at a dose of 25 mg/kg in mice bearing H460-DNp53 xenografts and mice bearing SW620 xenografts showed weak anti-cancer activity, but with Gemcitabine(60 mg/kg). The combined treatment of these two kinds of mice carrying transplanted tumor has strong anti-cancer activity. AZD7762 in combination with gemcitrate (10 mg/kg) inhibited tumor volume in rats bearing H460-DNp53 xenografts in a dose-dependent manner. The combination of AZD7762 (25 mg/kg) and Irinotecan (25 or 50 mg/kg) in mice bearing SW620 xenografts caused total tumor regression. at a dose of 25 mg/kg, AZD7762 showed weak anticancer activity in mice bearing H460-DNp53 xenografts and SW620 xenografts, however, the combination treatment with gemcitrate (60 mg/kg) has strong anti-cancer activity in both mice bearing transplanted tumors. AZD7762 in combination with gemcitrate (10 mg/kg) inhibited tumor volume in rats bearing H460-DNp53 xenografts in a dose-dependent manner. The combination of AZD7762 (25 mg/kg) and Irinotecan (25 or 50 mg/kg) in mice bearing SW620 xenografts caused total tumor regression. |
3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide - Reference
| Reference Show more | 1: Mitchell JB, Choudhuri R, Fabre K, Sowers AL, Citrin D, Zabludoff SD, Cook JA. In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clin Cancer Res. 2010 Apr 1;16(7):2076-84. Epub 2010 Mar 16. PubMed PMID: 20233881; PubMed Central PMCID: PMC2851146. 2: McNeely S, Conti C, Sheikh T, Patel H, Zabludoff S, Pommier Y, Schwartz G, Tse A. Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase. Cell Cycle. 2010 Mar;9(5):995-1004. Epub 2010 Mar 14. PubMed PMID: 20160494. 3: Goteti K, Garner CE, Utley L, Dai J, Ashwell S, Moustakas DT, Gönen M, Schwartz GK, Kern SE, Zabludoff S, Brassil PJ. Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Cancer Chemother Pharmacol. 2010 Jul;66(2):245-54. Epub 2009 Oct 16. PubMed PMID: 19841922. 4: Wagner JM, Karnitz LM. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol Pharmacol. 2009 Jul;76(1):208-14. Epub 2009 Apr 29. PubMed PMID: 19403702; PubMed Central PMCID: PMC2701464. |
3-[(Aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.759 ml | 13.796 ml | 27.592 ml |
| 5 mM | 0.552 ml | 2.759 ml | 5.518 ml |
| 10 mM | 0.276 ml | 1.38 ml | 2.759 ml |
| 5 mM | 0.055 ml | 0.276 ml | 0.552 ml |
Last Update：2024-01-02 23:10:35
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Product Name: AZD7762 Visit Supplier Webpage Request for quotationCAS: 860352-01-8
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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