WRN-IN-27
WRN-IN-27 is a potent, selective and orally active Werner syndrome RecQ helicase (WRN) inhibitor. WRN-IN-27 inhibits WRN with IC50 values of 20.0 nM and 43.2 nM in the ADP-Glo kinase assay and fluorometric helicase assay, respectively. WRN-IN-27 inhibits MSI-H cell growth selectively (GI50 = 61.8-440 nM), and exhibits antitumor activity in the colon cancer model for MSI-H tumor research.
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- 分子式: C33H29ClF3N9O6
- 分子量:740.09
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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生物活性
製品説明
Cellular Effect
体外実験
WRN-IN-27 (Q15) inhibits Werner syndrome RecQ helicase (WRN), with IC50 values of 20.0 nM and 43.2 nM in the ADP-Glo kinase assay and fluorometric helicase assay, respectively[1].
WRN-IN-27 directly binds WRN with a KD of 189 nM and demonstrates excellent isoform selectivity for WRN[1].
WRN-IN-27 (96 h) selectively inhibits the growth of MSI-H HCT 116, ISHIKAWA, RKO, and LoVo cells, with GI50 values of 61.8 nM, 440 nM, 308 nM, and 211 nM, respectively, and shows no inhibitory effect on MSS CaCo-2, AGS, LS513, and SW620 cells[1].
WRN-IN-27 (0.1-1 μM; 48 h) leads to a marked and concentration-dependent increase in γH2A.X and p21 levels in MSI-H HCT 116 and SW48 cells.[1].
WRN-IN-27 (1 μM; 24 h) selectively induces G2/M phase arrest in MSI-H HCT 116 and SW48 cells, but not in MSS CaCo-2 and SW620 cells[1].
WRN-IN-27 exhibits low hERG inhibitory activity, with an IC50 of 19.6 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT 116, SW48, CaCo-2, SW620 cells
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Concentration:0.1 μM, 0.5 μM, 1 μM
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Incubation Time:48 h
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Result:Led to a marked and concentration-dependent increase in γH2A.X and p21 levels in MSI-H HCT 116 and SW48 cells.
Did not increase γH2A.X and p21 levels in MSS CaCo-2 and SW620 cells.
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Cell Line:HCT 116, SW48, CaCo-2, SW620 cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Selectively induced G2/M phase arrest in MSI-H HCT 116 and SW48 cells.
Did not induce G2/M phase arrest in MSS CaCo-2 and SW620 cells.
Parmacokinetics
体内実験
WRN-IN-27 (10-40 mg/kg; p.o.; once daily; 33 days) suppresses tumor growth, achieves complete tumor regression at 40 mg/kg, and induces γH2A.X and p21 upregulation and Werner syndrome RecQ helicase (WRN) degradation in an MSI-H SW48 xenograft BALB/c nude mouse model[1].
WRN-IN-27 (10-40 mg/kg; p.o.; once daily; 33 days) triggers DNA damage and induces cell-cycle arrest and mitotic blockade in SW48 tumor tissues[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c mice were randomly divided into four groups, with five mice in each group[1].
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Dosage:125 mg/kg, 250 mg/kg, 500 mg/kg
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Administration:Oral administration (p.o.); single administration
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Result:Showed no adverse effects or abnormalities within 48 h after single administration.
Did not change body weight during the 2-week observation period.
Did not affect major organ weights, including heart, liver, spleen, lung, and kidney, after 2 weeks.
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Animal Model:Female 6-8-week-old BALB/c nude mice were subcutaneously engrafted with SW48 cells, randomized when the mean tumor volume reached approximately 150 mm3 [1].
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Dosage:10 mg/kg, 20 mg/kg, 40 mg/kg
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Administration:Oral gavage (p.o.); once daily; 33 days
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Result:Dose-dependently suppressed tumor growth in an MSI-H SW48 xenograft BALB/c nude mouse model, with TGI values of 43.3%, 76.6%, and 107% at 10, 20, and 40 mg/kg, respectively.
Achieved complete tumor regression at 40 mg/kg without body-weight loss.
Dose-dependently increased γH2A.X and p21 protein levels and induced Werner syndrome RecQ helicase (WRN) degradation in SW48 tumor tissues.
Increased CDKN1A and GDF15 mRNA levels and decreased CENPA and KIF20A mRNA levels.
Triggered DNA damage and induced cell-cycle arrest and mitotic blockade in SW48 tumor tissues.
- Kinase activity and phosphorylation assays
- Protocol for Cell Counting and Cell Density Analysis
- Somatic Cell Culture
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Kinase activity and phosphorylation assays
- Cell Counting-Based Growth Curve Assay
- MTT Cell Proliferation Assay
- Subcutaneous Cell-Line-Derived Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
化学情報
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分子量 740.09
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分子式 C33H29ClF3N9O6
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SMILES
O=C1C(N2CCN(CC2)C(C3=NC=NC(C)=C3O)=O)=C(N(C4=NC(C5=CC=C6C(OCO6)=C5)=NN41)CC(NC7=CC=C(C=C7Cl)C(F)(F)F)=O)CC
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. 1. Sui Q, Wang D, Hou H, Shi C, Cai X, Zhou Y, Cui R, Li M, Liu J, Teng D, Qin C, Zhang S, Zheng M. Structure-Guided Discovery of Potent, Selective, and Orally Bioavailable Werner Syndrome RecQ Helicase Inhibitors for the Treatment of Microsatellite Instability-High Tumors. J Med Chem. 2026 Jun 25;69(12):14492-14512. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
WRN-IN-27 関連分類
HY-184427 関連分類
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