Nilotinib

641571-10-0

C28H22F3N7O

DMSO : 6 mg/mL (11.33 mM; Need ultrasonic); H2O : < 0.1 mg/mL (insoluble)

Protein Tyrosine Kinase/RTK; Autophagy

Nilotinib is a second generation tyrosine kinase inhibitor (TKI), is significantly more potent against BCR-ABL than Imatinib, and is active against many Imatinib-resistant BCR-ABL mutants. IC50 & Target: Bcr-Abl^[1] In Vitro: The novel, selective Abl inhibitor, Nilotinib (AMN107), is designed to interact with the ATP-binding site of BCR-ABL with a higher affinity than Imatinib. In addition to being significantly more potent compared with Imatinib (IC₅₀<30 nM), Nilotinib also maintains activity against most of the BCR-ABL point mutants that confer Imatinib resistance^[1]. Nilotinib demonstrates significant antitumor efficacy against GIST xenograft lines and Imatinib-resistant GIST cell lines. The parent cell lines GK1C and GK3C show Imatinib sensitivity with IC₅₀ of 4.59+/-0.97 uM and 11.15+/-1.48 uM, respectively. The Imatinib-resistant cell lines GK1C-IR and GK3C-IR show Imatinib resistance with IC₅₀ values of 11.74+/-0.17 uM (P<0.001) and 41.37+/-1.07 uM (P<0.001), respectively^[2]. In Vivo: The percentage of tumor growth inhibition (TGI) is 83.8% for Imatinib and 69.6% for Nilotinib in the GK1X xenograft line (n.s.). In the GK2X xenograft line, TGI is 83.0% for Imatinib and 85.3% for Nilotinib (n.s.). Additionally, the GK3X xenograft line TGI is 31.1% for Imatinib and 47.5% for Nilotinib (n.s.). These results suggest that, except for the GK1X xenograft line, Nilotinib shows equivalent or higher antitumor effects than Imatinib^[2]. Nilotinib has a significant healing effect on the macroscopic and microscopic pathologic scores and ensures considerable mucosal healing in the indomethacin-induced enterocolitis rat model. While Nilotinib decreased the PDGFR alpha and beta levels and apoptotic scores in the colon, it did not have a significant effect on the weight and TNF-alpha levels. Further experimental investigations could provide more definitive evidence for humans^[3].