BRSD-143
BRSD-143 is an orally active KRASG12D inhibitor, with a Kd value of 0.003 nM for KRASG12D and 0.024 nM for KRASG12V. BRSD-143 inhibits the activity of phosphorylated ERK in KRAS-mutated cells. BRSD-143 induces tumor regression in ovarian cancer xenograft mouse models. BRSD-143 can be used for the research of KRAS-mutated cancers.
For research use only. We do not sell to patients.
- CAS No.: 3101973-42-3
- Formula: C35H37F3N6O4
- Molecular Weight:662.70
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
KRas G12D 0.003 nM (Ki) |
KRas G12V 0.024 nM (Ki) |
In Vitro
BRSD-143 (Compound 12) binds to KRASG12D with a Kd of 0.003 nM and to KRASG12V with a Kd of 0.024 nM, exhibiting exceptional high-affinity interactions with both mutant KRAS proteins[1].
BRSD-143 has a low efflux permeability of 15.4 ×10−6 cm/s in MDCK cells, with intrinsic clearance values of 338 μL/min/mg in human liver microsomes and 542 μL/min/mg in mouse liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:RKN tumor bearing SCID-Beige mice[1]
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Dosage:0.3-3 mg/kg
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Administration:p.o.; once daily; 2 weeks
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Result:Inhibited RKN tumor growth in a dose-dependent manner, with tumor inhibition of 38.8%, tumor
regression of -45.2% and -89.4% across 0.3, 1 and 3 mpk dose, respectively.
Were well tolerated without body weight loss[1].
Chemical Information
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CAS No. 3101973-42-3
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Molecular Weight 662.70
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Formula C35H37F3N6O4
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SMILES
C[C@@]12CCCN(C3=NC(OC[C@@]45CCCN4C[C@@H](C5)F)=NC6=C(C(C7=CC(O)=CC8=CC=C(C(CCCOC(N2)=O)=C78)F)=NC=C36)F)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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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)