Nilotinib monohydrochloride monohydrate is a selective Abl inhibitor designed to interact with the ATP-binding site of BCR-ABL with higher affinity than Imatinib, while being more effective (IC50 < 30 nM) and retaining activity against most BCR-ABL point mutants that confer resistance to Imatinib[1]. Nilotinib monohydrochloride monohydrate exhibits significant antitumor efficacy against GIST xenograft cell lines and Imatinib-resistant GIST cell lines. The parent cell lines GK1C and GK3C demonstrate sensitivity to Imatinib, with IC50 values of 4.59±0.97 µM and 11.15±1.48 µM, respectively. The Imatinib-resistant cell lines GK1C-IR and GK3C-IR exhibit resistance to Imatinib, with IC50 values of 11.74±0.17 µM and 41.37±1.07 µM, respectively[2].
Nilotinib monohydrochloride monohydrate 动物研究
Animal study
Administered orally via gavage at 40 mg/kg daily for 4 weeks, Nilotinib monohydrochloride monohydrate demonstrates equivalent or greater antitumor activity in GIST xenografted BALB/cSLc-nu/nu mice[2]. Nilotinib monohydrochloride monohydrate significantly improves macroscopic and microscopic pathology scores, ensuring good mucosal healing in a rat model of indomethacin-induced small intestinal colitis, while also reducing levels of PDGFRα and β, as well as apoptosis scores in the colon[3]. Administered orally via gavage at a dose of 40 mg/kg once daily for 4 weeks, Nilotinib monohydrochloride monohydrate achieves tumor growth inhibition rates in GIST xenografted BALB/cSLc-nu/nu mice of 69.6% in GK1X, 85.3% in GK2X, and 47.5% in the GK3X xenograft cell line[2].
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