nazartinib   Click here for help

GtoPdb Ligand ID: 9204

Synonyms: compound 47 [PMID: 27433829] | EGF-816 | EGF816
Compound class: Synthetic organic
Comment: EGF816 is an irreversible and selective inhibitor of EGFRs harbouring gatekeeper T790M, and sensitising L858R mutations, whilst sparing the wild-type receptor (such compounds are termed third generation EGFR tyrosine kinase inhibitors) [3]. It has been developed to overcome acquired resistance to, and side-effect liabilities of first and second generation EGFR inhibitors in non-small-cell lung cancer (NSCLC). Small-molecule EGFR T790M inhibitors and the development of novel compounds in the discovery pipeline are reviewed by Song et al. (2016) [5].
EGF816 is claimed in Novartis' patent WO2015085482 [4], where it is named (R,E)-N-(7-chloro-l-(l-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-lH-benzo[d]imidazol-2-yl)-2-methylisonicotinamide, which resolves to the IUPAC name presented here.
Preclinical characterisation is reported in [1].
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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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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 1
Rotatable bonds 8
Topological polar surface area 83.36
Molecular weight 494.22
XLogP 3.44
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 CN(CC=CC(=O)N1CCCCC(C1)n1c(NC(=O)c2ccnc(c2)C)nc2c1c(Cl)ccc2)C
Isomeric SMILES CN(C/C=C/C(=O)N1CCCC[C@H](C1)n1c(NC(=O)c2ccnc(c2)C)nc2c1c(Cl)ccc2)C
InChI InChI=1S/C26H31ClN6O2/c1-18-16-19(12-13-28-18)25(35)30-26-29-22-10-6-9-21(27)24(22)33(26)20-8-4-5-15-32(17-20)23(34)11-7-14-31(2)3/h6-7,9-13,16,20H,4-5,8,14-15,17H2,1-3H3,(H,29,30,35)/b11-7+/t20-/m1/s1
InChI Key IOMMMLWIABWRKL-WUTDNEBXSA-N
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Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel