Nilotinib D6

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)