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Synonyms: AMN 107 | AMN107 | Tasigna®
nilotinib is an approved drug (FDA & EMA (2007))
Compound class: Synthetic organic
Comment: Nilotinib is a Type-2 kinase inhibitor and was first approved by the FDA in 2007.
Preclinical studies in rodent Parkinson's disease models suggest that nilotinib has some potential to promote autophagic degradation of α-synuclein [4-6,9], a brain protein whose accumulation and aggregation contributes to the formation of toxic insoluble fibrils which cause pathological changes such as neuronal loss in Parkinson's disease and other synucleinopathies. This mechanism has been evaluated in a pilot, proof-of-concept and safety clinical trial in a small number of patients with Parkinson's disease- and diffuse Lewy body disease-associated cognitive impairment (see NCT02281474; note that this trial is not placebo controlled or blinded).
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
View more information in the IUPHAR Pharmacology Education Project: nilotinib
|No information available.
|Summary of Clinical Use
|Used in the treatment of chronic myelogenous leukemia.
Marketed formulations contain nilotinib hydrochloride monohydrate (PubChem CID 16757572).
|Mechanism Of Action and Pharmacodynamic Effects
|Nilotinib is a potent inhibitor of the ABL tyrosine kinase activity of the BCR-ABL oncoprotein both in cell lines and in primary Philadelphia-chromosome positive leukemia cells. The substance binds with high affinity to the ATP-binding site of wild-type and 32/33 imatinib-resistant mutant forms of BCR-ABL. Nilotinib also targets c-Kit and PDGFR but has little or no effect against the majority of other protein kinases examined, including Src.
|Peak concentrations of nilotinib are reached 3 hours after oral administration. Plasma protein binding is approximately 98%. Bioavailability of nilotinib is increased if administered after food.
|Nilotinib is primarily metabolised by CYP3A4, with possible minor contribution from CYP2C8. None of the metabolites contribute significantly to the pharmacological activity of nilotinib.
|More than 90% of the dose is eliminated within 7 days, mainly in feces.
|Pharmacokinetics of nilotinib are not significantly affected by age, body weight, race, or gender.
|Organ function impairment
|The effect of renal function impairment on the pharmacokinetics of nilotinib has not been investigated. Total exposure to nilotinib is increased with hepatic function impairment.
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)