Mechanism of action: Neurotrophic tyrosine kinase receptor (NTRK; or Tropomycin-related kinase,Trk) inhibitor
AZD1332 inhibits TrkA/B in an ATP-competitive manner with a potency of <10nM. It inhibits phosphorylation of TrkA/B/C in MCF10A cells overexpressing TrkA and NIH3T3 cells over expressing TrkA, TrkB, or TrkC with a potency of ≤5nM. The EC50 of AZD1332 was ~2nM in a panel of Baf3 survival assays driven by TrkA, TrkB, or TrkC.
In xenograft studies with 3T3-TrkA-∆ allograft models, 50mg/kg QD or BID AZD1332, by oral gavage, led to (%T/C) = -64 and -65, respectively. AZD1332 is well tolerated up to 110mg/kg twice daily for 14 days with minimal body weight loss (<5%). In a disease-relevant model of NOD/SCID/IL2R-gamma immunocompromised mice injected with SK-N-SH cells, treated with 100mg/kg by oral gavage twice daily for 12 days led to a (%T/C) = 2.6%.
Publications for this compound
Find out more about this compound by reading related Publications:
Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway.
Gene information from the NCBi
This compound works on the following genes: