nilotinib   Click here for help

GtoPdb Ligand ID: 5697

Synonyms: AMN 107 | AMN107 | Tasigna®
Approved drug PDB Ligand
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).
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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.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: nilotinib

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 97.1
Molecular weight 529.18
XLogP 4.93
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Cc1ncn(c1)c1cc(NC(=O)c2ccc(c(c2)Nc2nccc(n2)c2cccnc2)C)cc(c1)C(F)(F)F
Isomeric SMILES Cc1ncn(c1)c1cc(NC(=O)c2ccc(c(c2)Nc2nccc(n2)c2cccnc2)C)cc(c1)C(F)(F)F
InChI InChI=1S/C28H22F3N7O/c1-17-5-6-19(10-25(17)37-27-33-9-7-24(36-27)20-4-3-8-32-14-20)26(39)35-22-11-21(28(29,30)31)12-23(13-22)38-15-18(2)34-16-38/h3-16H,1-2H3,(H,35,39)(H,33,36,37)
InChI Key HHZIURLSWUIHRB-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Used in the treatment of chronic myelogenous leukemia.
Marketed formulations contain nilotinib hydrochloride monohydrate (PubChem CID 16757572).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
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.
Pharmacokinetics Click here for help
Absorption/Distribution
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.
Biotransformation/Metabolism
Nilotinib is primarily metabolised by CYP3A4, with possible minor contribution from CYP2C8. None of the metabolites contribute significantly to the pharmacological activity of nilotinib.
Elimination
More than 90% of the dose is eliminated within 7 days, mainly in feces.
Population pharmacokinetics
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.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)