DZX19
DZX19 (Compound C02) is an orally active, selective TRK inhibitor with a TRKA IC50 value of 1.32 nM, a TRKB IC50 of 2.28 nM, and a TRKC IC50 of 4.05 nM. DZX19 inhibits the kinase activities of wild-type TRKA, TRKA mutants (G595R, F589L, G667C), wild-type TRKB, and wild-type TRKC, and suppresses the phosphorylation of TRKA as well as its downstream AKT and ERK signaling pathways. DZX19 induces apoptosis. DZX19 inhibits tumor growth in a colorectal cancer xenograft mouse model. DZX19 is applicable for the research of colorectal cancer.
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- Formule: C20H18F2N4O2S
- Masse moléculaire:416.44
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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TrkA 1.32 nM (IC50) |
TrkB 2.28 nM (IC50) |
TrkC 4.05 nM (IC50) |
TRKAG595R 16.56 nM (IC50) |
TRKAF589L 74.37 nM (IC50) |
TRKAG667C 60.18 nM (IC50) |
DZX19 (C02) (72 h) potently inhibits the proliferation of TRK fusion-positive and TRKA mutant-harboring cell lines, with greater efficacy than Entrectinib, and exhibits minimal off-target activity in TRK-negative A549 cells[1].
DZX19 (C02) (7.5-15 nM; 14 days) strongly suppresses the long-term colony-forming ability of TRK fusion-positive Km-12 cells more effectively than Entrectinib[1].
DZX19 (C02) (7.5-15 nM; 48 h) potently inhibits the migration of TRK fusion-positive Km-12 cells more effectively than Entrectinib[1].
DZX19 (C02) (7.5-30 nM; 24 h) dose-dependently induces G1 cell cycle arrest in TRK fusion-positive Km-12 cells, with stronger activity than Entrectinib[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Km-12
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Concentration:7.5-30 nM
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Incubation Time:24 h
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Result:Induced a dose-dependent increase in the G1 phase ratio of Km-12 cells: 46.7% at 7.5 nM, 59.1% at 15 nM, and 66.2% at 30 nM.
Caused a corresponding decrease in the S phase ratio.
Showed more potent G1/S phase transition inhibition than Entrectinib at the same concentrations.
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Cell Line:Km-12
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Concentration:7.5-30 nM
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Incubation Time:48 h
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Result:Induced dose-dependent apoptosis in Km-12 cells, with apoptotic rates of 16.6% at 7.5 nM, 26.8% at 15 nM, and 36.6% at 30 nM (compared to 9.64% in the DMSO control).
Showed stronger pro-apoptotic activity than Entrectinib at the same concentrations.
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Cell Line:Km-12
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Concentration:7.5, 15, 30 nM
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Incubation Time:6 h
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Result:Suppressed the phosphorylation of TRKA, ERK, and AKT in a dose-dependent manner..
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | AUCinf | CL | MRT | Vss | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 40 mg/kg | p.o. | 2.32 h | 3.25 h | 3437 ng/mL | 21354 ng·h/mL | 21377 ng·h/mL | / | 5.00 h | / | 172.9 % |
| Rat[1] | 20 mg/kg | p.o. | 2.05 h | 2.67 h | 1250 ng/mL | 7148 ng·h/mL | 7705 ng·h/mL | / | 4.68 h | / | 124.6 % |
| Rat[1] | 1 mg/kg | i.v. | 1.43 h | 0.083 h | 455 ng/mL | 300 ng·h/mL | 309 ng·h/mL | 51.9 mL/min/kg | 1.14 h | 3551 mL/kg | / |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c-nu (female; subcutaneous xenograft model injected with 5×106 Km-12 cells)[1]
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Dosage:20 mg/kg; 40 mg/kg
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Administration:p.o.; daily
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Result:Achieved a tumor growth inhibition (TGI) rate of 60.2% at 20 mg/kg.
Achieved a tumor growth inhibition (TGI) rate of 82.7% at 40 mg/kg.
Caused no significant loss of body weight during the treatment period.
Showed no significant drug-induced toxicity via H&E staining of major organs (heart, liver, spleen, lungs, kidneys).
Chemical Information
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Masse moléculaire 416.44
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Formule C20H18F2N4O2S
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SMILES
NC(C1=C(SC=C1C2=CC(NCC3=CC(F)=CC(F)=C3)=CC=C2)NC(NC)=O)=O
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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.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DZX19 Related Classifications
HY-181871 Related Classifications
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