TRK-IN-21

TRK-IN-21 (5n) is an orally activity TRK inhibitor. TRK-IN-21 inhibits TRKAWT, TRKAG667C, TRKAF589L, and TRKAG595 with IC50s of 0.3, 2.3, 0.4 and 0.5 nM, respectively. TRK-IN-21 can be used for the research of cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Trk Receptor

IC50: 0.3 nM (TRKAWT), 2.3 nM (TRKAG667C), 0.4 nM (TRKAF589L), 0.5 nM (TRKAG595)[1]

TRK-IN-21 (30-100 mg/kg; p.o. twice daily for 11-14 days) inhibits tumor growth in Ba/F3-TRKA xenograft models[1]. 1.19Pharmacokinetic Properties of TRK-IN-21 in Rats and Dogs[1]. Rats IV 1 mg/kg Rats IV 5 mg/kg Dogs IV 2 mg/kg Dogs PO 10 mg/kg Cmax (ng/mL) 231.2 93.5 1063.8 2070.1 Tmax (h) 0.1 1.7 0.3 AUClast (ng·h/mL) 456.1 588.6 6923.0 24305.2 CL (L/h/kg) 2.1 8.0 0.2 0.3 T1/2 (h) 2.2 2.2 15.2 15.3 Vz (L/kg) 6.7 25.7 4.2 6.2 MRT (h) 2.5 4.0 8.2 8.8 F (%) 26 30.2 71 Animal Model: 6-week-old BALB/cA nude mice with Ba/F3-TRKA xenografts[1] Dosage: 30 and 100 mg/kg Administration: Oral gavage; 30 and 100 mg/kg twice daily; for 11-14 days Result: Dose-dependently inhibited BaF3-TMP3-TRKAWT-transfected tumor progression with a tumor growth inhibition value of 97%, showed a better potency to larotrectinib at the same dosage. Inhibited BaF3-LMNA-TrkAG667C-transfected tumor progression with a tumor growth inhibition value of 73%, showed a better potency to selitrectinib at the same dosage.

[1]. Gong Y, et al. Discovery of 3-pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine derivatives as potent TRK inhibitors to overcome clinically acquired resistance. Eur J Med Chem. 2022 Aug 5;241:114654.