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 TRKA^G595R and TRKA^G667C, respectively. TRK-IN-34 inhibits the kinase activities of TRKA^G595R and TRKA^G667C 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 TRKA^G667C mutation^[1].

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 TRKA^G595R, TRKA^G667C, TRKC^G623R and TRKA^F589L 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.

TRK-IN-34 (compound 5c) (30-60 mg/kg; p.o.; twice daily; 2 weeks) exhibits potent, dose-dependent antitumor efficacy in Ba/F3-LMNA-TRKAG^667C xenograft mice, with 91% TGI at 30 mg/kg and 115% TGI plus partial regression in 4/6 animals at 60 mg/kg^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

420.36

C₁₉H₁₆F₄N₆O

2489327-91-3

FC1=CC=C(OCC(F)(F)F)C([C@@H](C)NC2=NC3=C(C4=CNN=C4)C=NN3C=C2)=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Liu ZR, et al. Discovery of new non-macrocyclic TRK inhibitors based on conformational flexibility and scaffold hopping to overcome clinical acquired resistance. Bioorg Chem. 2026;172:109603.  [Content Brief]