TRK-IN-34
TRK-IN-34 is an orally active TRKand TRKC mutant kinase inhibitor, with IC50 values of 0.75 nM and 0.96 nM against TRKAG595R and TRKAG667C, respectively. TRK-IN-34 inhibits the kinase activities of TRKAG595R and TRKAG667C at the functional level. TRK-IN-34 inhibits the proliferation of TRKA-transfected cells, exerts tumor growth-inhibitory effects and achieves partial tumor regression in xenograft models. TRK-IN-34 can be used to study TRK inhibitor-resistant cancers driven by the TRKAG667C mutation.
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- CAS. Nr.: 2489327-91-3
- Formel: C19H16F4N6O
- Molecular Weight:420.36
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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
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TRKAG595R 0.75 nM (IC50) |
TRKAG667C 0.96 nM (IC50) |
TRKAF589L 0.44 nM (IC50) |
TrkA 2.8 nM (IC50) |
TrkCG623R 0.73 nM (IC50) |
TrkCG696A 1.3 nM (IC50) |
TRK-IN-34 (compound 5c) shows satisfactory metabolic stability in human liver microsomes with a long half-life of 153.1 min[1].
TRK-IN-34 (3 days) potently inhibits the proliferation of Ba/F3 cells expressing wild-type or mutant TRKA fusion proteins. Its IC50 values against CD74-NTRK1-WT, CD74-NTRK1-G595R, and CD74-NTRK1-G667C are 3 nM, 6 nM, and 17 nM, respectively[1].
TRK-IN-34 (1.23-300 nM; 6 h) dose-dependently inhibits the phosphorylation of TRKA and its downstream signaling proteins PLCγ1 and ERK in Ba/F3 cells expressing wild-type or mutant TRKA fusion proteins after 6 h of treatment[1].
TRK-IN-34 potently inhibits wild-type and mutant TRK kinases in a cell-free enzymatic assay. The IC50 values for key drug-resistant mutants such as TRKAG595R, TRKAG667C, TRKCG623R and TRKAF589L are 0.75 nM, 0.96 nM, 0.73 nM and 0.44 nM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3-CD74-NTRK1-WT, Ba/F3-CD74-NTRK1-G595R, and Ba/F3-CD74-NTRK1-G667C cells
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Concentration:1.23, 3.7, 11.1, 33.3, 100 nM (Ba/F3-CD74-NTRK1-WT and Ba/F3-CD74-NTRK1-G595R cells); 3.7, 11, 33, 100, 300 nM (Ba/F3-CD74-NTRK1-G667C cells)
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Incubation Time:6 h
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Result:Reduced phosphorylation of TRKA, PLCγ1, and ERK in a dose-dependent manner across all three Ba/F3 cell lines (wild-type, G595R mutant, G667C mutant).
| Species | Dose | Route | T1/2 | Cmax | AUC0-inf | CL | Tmax | F |
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| Rat[1] | 1 mg/kg | i.v. | 5.0 h | 174.2 ng/mL | 563.7 ng·h/mL | 1.8 L/h/kg | / | / |
| Rat[1] | 5 mg/kg | i.g. | 4.0 h | 282.7 ng/mL | 1485.1 ng·h/mL | / | 2.0 h | 56.2 % |
| Dog[1] | 1 mg/kg | i.v. | 6.0 h | 628.9 ng/mL | 1557.0 ng·h/mL | 0.68 L/h/kg | / | / |
| Dog[1] | 5 mg/kg | i.g. | 6.8 h | 564.3 ng/mL | 4214.2 ng·h/mL | / | 1.7 h | 52.7 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Ba/F3-LMNA-TRKAG667C xenograft[1]
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Dosage:30 mg/kg; 60 mg/kg
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Administration:p.o.; twice daily; 2 weeks
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Result:Achieved a tumor growth inhibition (TGI) of 91% at 30 mg/kg.
Achieved a TGI of 115% with partial tumor regression observed in 4 out of 6 animals at 60 mg/kg.
Chemical Information
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CAS. Nr. 2489327-91-3
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Molecular Weight 420.36
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Formel C19H16F4N6O
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SMILES
FC1=CC=C(OCC(F)(F)F)C([C@@H](C)NC2=NC3=C(C4=CNN=C4)C=NN3C=C2)=C1
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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.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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