MSC778
MSC778 is an effective and orally active flap endonuclease 1 (FEN1) inhibitor with an IC50 of 3 nM and a KD of 2.9 nM. MSC778 exhibits 145-fold, 516-fold, and 65-fold selectivity over EXO1, GEN1, and XPG, respectively. MSC778 selectively kills BRCA2-deficient cells and potentiates the activity of Niraparib (HY-10619) to induce tumor stasis in a BRCA2 KO DLD-1 mouse xenograft. MSC778 can be used in the research of colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 3098173-17-9
- Formula: C22H20ClN3O5
- Molecular Weight:441.86
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
MSC778 (7 days) selectively kills BRCA2 knockout DLD-1 cells, with an EC50 value of 210 nM (apparent value) and the free EC50 (EC50,ub) after protein binding correction is 11 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC | F |
|---|---|---|---|---|---|
| Dog[1] | 0.2 mg/kg | i.v. | 1240 ng/mL | 2520 ng·h/mL | / |
| Dog[1] | 16 mg/kg | p.o. | 6000 ng/mL | 43200 ng·h/mL | 21 % |
| Mice[1] | 0.2 mg/kg | i.v. | 2490 ng/mL | 8510 ng·h/mL | / |
| Mice[1] | 10 mg/kg | p.o. | 6030 ng/mL | 56900 ng·h/mL | 16 % |
| Mice[1] | 30 mg/kg | p.o. | 30500 ng/mL | 229536 ng·h/mL | 16 % |
| Rat[1] | 0.2 mg/kg | i.v. | 1950 ng/mL | 2240 ng·h/mL | / |
| Rat[1] | 10 mg/kg | p.o. | 5860 ng/mL | 27400 ng·h/mL | 15 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BRCA2 KO DLD-1 cells xenograft model established in Balb/c nude, female mice[1]
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Dosage:100 mg/kg with or without Niraparib
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Administration:Oral gavage (i.g.), twice daily for 28 days
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Result:Observed no tumor growth inhibition (TGI) with the single-agent treatment. Achieved 93% TGI in the combined treatment group, resulting in tumor stasis. No weight loss or clinical signs of toxicity.
Chemical Information
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CAS No. 3098173-17-9
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Molecular Weight 441.86
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Formula C22H20ClN3O5
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SMILES
ClC1=CC2=CC([C@@H](OC3=NN(C[C@@H](COCC4)N4C5=O)C5=C(O)C3=O)C)=CC=C2C=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)