Nilotinib-d6 is intended for use as an internal standard for the quantification of nilotinib by GC- or LC-MS. Nilotinib is an inhibitor of wild-type and mutant Bcr-Abl (IC50s = 15 and 9-400 nM, respectively).1 It is selective for wild-type and mutant Bcr-Abl over Src and LYN (IC50s = >5,000 nM for both). Nilotinib inhibits Bcr-Abl autophosphorylation and cell proliferation in Ba/F3 cells expressing wild-type or mutant Bcr-Abl (IC50s = 7-155 and 13-51 nM, respectively). In vivo, nilotinib (1 mg/kg) reduces midbrain Bcr-Abl autophosphorylation, amyloid-β levels, and neuronal loss, as well as improves autophagosome clearance and reverses cognitive deficits in the Tg2576 transgenic mouse model of Alzheimer’s disease.2 It also reduces serum creatine levels, renal profibrotic gene expression, and tubulointerstitial damage, as well as increases survival in a rat model of 5/6 nephrectomy-induced chronic kidney disease.3 Formulations containing nilotinib have been used in the treatment of leukemia.
1.O'Hare, T., Walters, D.K., Stoffregen, E.P., et al.In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutantsCancer Res.65(11)4500-4505(2005) 2.La Barbera, L., Vedele, F., Nobili, A., et al.Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer's DiseaseProg. Neurobiol.202102031(2021) 3.Iyoda, M., Shibata, T., Hirai, Y., et al.Nilotinib attenuates renal injury and prolongs survival in chronic kidney diseaseJ. Am. Soc. Nephrol.22(8)1486-1496(2011)