PROTAC c-Met degrader-3
PROTAC c-Met degrader-3 is a c-Met PROTAC degrader with a DC50 of 0.59 nM. PROTAC c-Met degrader-3 induces ubiquitination and degradation of c-Met. PROTAC c-Met degrader-3 induces Apoptosis. PROTAC c-Met degrader-3 can be used in lung cancer-related research.
(Pink: c-Met ligand (HY-14721); Blue: Cereblon ligand (HY-W249500); Black: linker).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Formel: C51H54N10O7
- Molecular Weight:919.04
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
Cereblon |
c-Met 0.59 nM (DC50) |
In Vitro
PROTAC c-Met degrader-3 (Compound 22b) (0.03-1000 nM; 24 h) potently degrades c-Met in EBC-1 lung cancer cells, with a DC50 of 0.59 nM, and the maximum degradation rate reaches 96.14% at 15.6 nM[1].
PROTAC c-Met degrader-3 (15.6 nM; 3-72 h) induces time-dependent degradation of c-Met in EBC-1 lung cancer cells, with a maximum degradation rate of up to 93.13% after treatment at 15.6 nM for 72 h[1].
PROTAC c-Met degrader-3 potently inhibits the proliferation of c-Met-sensitive EBC-1 and Hs746T cancer cells, with IC50 values of 4 nM and 8 nM, respectively, while shows weak activity in c-Met-insensitive A549 and HCT116 cells[1].
PROTAC c-Met degrader-3 (3.9-15.6 nM; 7 days) significantly inhibits colony formation of EBC-1 lung cancer cells after 7 days of treatment at concentrations of 3.9, 7.8 and 15.6 nM[1].
PROTAC c-Met degrader-3 potently inhibits the proliferation of Tepotinib (HY-14721)-resistant MKN45 gastric cancer cells, with an IC50 value of 10 nM[1].
PROTAC c-Met degrader-3 (5-50 nM; 72 h) induces apoptosis in EBC-1 lung cancer cells, and mainly drives cells into the early apoptotic stage after treatment at 5, 15 or 50 nM for 72 h[1].
PROTAC c-Met degrader-3 (5-50 nM; 24 h) upregulates the expression of cleaved PARP and cleaved caspase-3 in EBC-1 lung cancer cells in a dose-dependent manner after 24 h of treatment, indicating that it induces apoptosis via these pathway markers[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:EBC-1 lung cancer cells
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Concentration:0.03-1000 nM
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Incubation Time:24 h
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Result:Dose-dependently degraded c-Met starting from 0.03 nM.
Achieved a maximum degradation rate (Dmax) of 96.14% at 15.6 nM.
Exhibited a DC50 of 0.59 nM.
Showed a hook effect at concentrations of 500 nM and 1000 nM.
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Cell Line:EBC-1 lung cancer cells
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Concentration:15.6 nM
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Incubation Time:3-72 h
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Result:Degraded c-Met in a time-dependent manner.
Reached maximal degradation (93.13%) at 72 h.
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Cell Line:EBC-1 lung cancer cells
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Concentration:5-50 nM
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Incubation Time:72 h
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Result:Induced apoptosis in EBC-1 cells.
Drove the majority of cells into early apoptosis at the tested concentrations.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | C0 | Cmax | AUC0-t | AUC0-∞ | Vss | Vz | CL | MRT0-t | MRT0-∞ | F |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 2 mg/kg | i.v. | 6.90 h | 0.0833 h | 1012.47 ng/mL | 2383.29 ng/mL | 531.98 ng·h/mL | 550.82 ng·h/mL | 36.26 L/kg | 13.13 L/kg | 60.78 mL/min/kg | 2.49 h | 3.58 h | / |
| Rat[1] | 5 mg/kg | i.p. | 5.49 h | 2.00 h | / | 104.35 ng/mL | 654.54 ng·h/mL | 677.67 ng·h/mL | / | / | / | 5.06 h | 6.00 h | 49.21 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (female, 4 weeks old, subcutaneous xenograft model via injection of 5×106 EBC-1 cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; once every 2 days
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Result:Reduced tumor volume by 60.28%.
Reduced tumor volume by 86.14%, which was superior to the equal dose of tepotinib (74.50% inhibition).
Showed no body weight loss in treated mice.
Exhibited no evident organ toxicity via H&E staining.
Induced dose-dependent tumor cell apoptosis and cell shrinkage via immunohistochemical analysis.
Chemical Information
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Molecular Weight 919.04
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Formel C51H54N10O7
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SMILES
O=C(N1)N(C2=CC(C(N3CCC4(CCN(CC4)C(CN5CCC(COC6=CN=C(N=C6)C7=CC=CC(CN8N=C(C=CC8=O)C9=CC(C#N)=CC=C9)=C7)CC5)=O)CC3)=O)=CC=C2OC)CCC1=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
PROTAC c-Met degrader-3 Related Classifications
HY-168910 Related Classifications
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