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

Large-scale screening data

DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,10
Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
discoidin domain receptor tyrosine kinase 1 DDR1 Hs Inhibitor Inhibition 9.0 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(H396P)-nonphosphorylated Hs Inhibitor Inhibition 8.3 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1-nonphosphorylated Hs Inhibitor Inhibition 8.0 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(Q252H)-nonphosphorylated Hs Inhibitor Inhibition 8.0 pKd
ZAK sterile alpha motif and leucine zipper containing kinase AZK ZAK Hs Inhibitor Inhibition 8.0 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(F317L)-nonphosphorylated Hs Inhibitor Inhibition 7.9 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1-phosphorylated Hs Inhibitor Inhibition 7.9 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(Y253F)-phosphorylated Hs Inhibitor Inhibition 7.9 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(F317L)-phosphorylated Hs Inhibitor Inhibition 7.8 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(M351T)-phosphorylated Hs Inhibitor Inhibition 7.8 pKd
Displaying the top 10 targets  View all targets in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,3
Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
EPH receptor B2 EphB2/EPHB2 Hs Inhibitor Inhibition 1.5
discoidin domain receptor tyrosine kinase 2 DDR2/DDR2 Hs Inhibitor Inhibition 1.8
ABL proto-oncogene 1, non-receptor tyrosine kinase Abl/ABL1 Hs Inhibitor Inhibition 3.5
ABL proto-oncogene 2, non-receptor tyrosine kinase Arg/ABL2(ARG) Hs Inhibitor Inhibition 4.9
EPH receptor B3 EphB3/EPHB3 Hs Inhibitor Inhibition 5.6
EPH receptor B1 EphB1/EPHB1 Hs Inhibitor Inhibition 10.6
EPH receptor A2 EphA2/EPHA2 Hs Inhibitor Inhibition 10.8
EPH receptor B4 EphB4/EPHB4 Hs Inhibitor Inhibition 11.4
B-Raf proto-oncogene, serine/threonine kinase nd/BRAF Hs Inhibitor Inhibition 11.5
EPH receptor A4 EphA4/EPHA4 Hs Inhibitor Inhibition 12.0
Displaying the top 10 targets  View all targets in screen »