TIY-7
TIY-7 is a selective and orally active tropomyosin receptor kinase (TRK) inhibitor. TIY-7 shows enzyme inhibitory activity with IC50s of 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM for TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, TRKCG696A, respectively. TIY-7 shows anti-tumor potency in mouse xenograft model.
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- CAS No.: 2846435-83-2
- Formule: C21H18F4N6O
- Masse moléculaire:446.40
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Activité biologique
Description
IC50 & Target
[1]|
TrkA 2.9 nM (IC50) |
TrkA |
TrkC |
In Vitro
TIY-7 (compound 12c) shows enzyme inhibitory activity with IC50s of 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM for TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, TRKCG696A, respectively[1].
TIY-7 (1 µM) shows selectivity with inhibitory rate of 62%, 99%, 11% for ALK, ROS1, and JAK1 kinase[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
TIY-7 (30 mg/kg; P.o.; twice daily for 12-14 consecutive days) inhibits tumor progression in a dose-dependent manner in xenograft model[1].
Pharmacokinetic Parameters of TIY-7 in Male Sprague-Dawley rats[1].
| Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | T1/2 (h) | CL (mL/min/kg) | F % | MRT0-t (h) | AUCtot (ng/mL·h) | AUCextra (%) | |
| ip mice | 9.103 | 2078 | 0.0833 | 0.8 | 154 | 86 | 0.7 | 982.3 | 1.3 |
| iv mice | 0.711 | 322.7 | 0.0833 | 1.1 | 133 | 0.9 | 88.8 | 15.2 | |
| iv dog | 26.76 | 272 (µg/mL) | 0.0833 | 3.8 | 0.69 | 3.8 | 654.7 (µg/mL·h) | 0.9 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley rats[1]
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Dosage:5 mg/kg for p.o.; 1 mg/kg for i.v.
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Administration:P.o. or i.v.
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Result:Showed good PK properties with an oral bioavailability (F) of 39.8%.
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Animal Model:6-week-old BALB/cA nude mice (BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft models)[1]
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Dosage:30 mg/kg (dissolved in 70% PEG400 and 30% water)
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Administration:P.o.; twice daily; 12-14 consecutive days
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Result:Dose-dependently inhibited tumor progression with the TGI of 95% and 86% in BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft model.
Chemical Information
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CAS No. 2846435-83-2
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Masse moléculaire 446.40
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Formule C21H18F4N6O
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SMILES
FC1=CC=C(C([C@H]2CCCN2C3=NC4=C(C=NN4C=C3)C5=CNN=C5)=C1)OCC(F)(F)F
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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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.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)