erlotinib   Click here for help

GtoPdb Ligand ID: 4920

Synonyms: NSC 718781 | OSI 744 | OSI-774 | R 1415 | Tarceva®
Approved drug PDB Ligand
erlotinib is an approved drug (FDA (2004), EMA (2005))
Compound class: Synthetic organic
Comment: Erlotinib is a clinically approved type-1 inhibitor of the epidermal growth factor receptor (EGFR) receptor tyrosine kinase. This drug shows some selectivity for EGFR exon 19 deletion or exon 21 L858R mutations over the wild type receptor.
Subsequent studies have shown erlotinib to be a potent inhibitor of JAK2V617F activity. JAK2V617F, a mutant from of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. Study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders. Specificity of inhibition with regard to other tyrosine kinase receptors remains to be fully characterized. Erlotinib is a Type-1 kinase inhibitor.
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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: erlotinib

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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Click here for structure editor
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 5
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 74.73
Molecular weight 393.17
XLogP 2.7
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 COCCOc1cc2c(ncnc2cc1OCCOC)Nc1cccc(c1)C#C
Isomeric SMILES COCCOc1cc2c(ncnc2cc1OCCOC)Nc1cccc(c1)C#C
InChI InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
InChI Key AAKJLRGGTJKAMG-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: 2,6
Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
epidermal growth factor receptor EGFR(L747-T751del,Sins) Hs Inhibitor Inhibition 9.5 pKd
epidermal growth factor receptor EGFR(L747-S752del, P753S) Hs Inhibitor Inhibition 9.3 pKd
epidermal growth factor receptor EGFR(E746-A750del) Hs Inhibitor Inhibition 9.3 pKd
epidermal growth factor receptor EGFR(G719S) Hs Inhibitor Inhibition 9.3 pKd
epidermal growth factor receptor EGFR(L747-E749del, A750P) Hs Inhibitor Inhibition 9.3 pKd
epidermal growth factor receptor EGFR Hs Inhibitor Inhibition 9.2 pKd
epidermal growth factor receptor EGFR(G719C) Hs Inhibitor Inhibition 9.1 pKd
epidermal growth factor receptor EGFR(L858R) Hs Inhibitor Inhibition 9.0 pKd
epidermal growth factor receptor EGFR(L861Q) Hs Inhibitor Inhibition 8.9 pKd
epidermal growth factor receptor EGFR(S752-I759del) Hs Inhibitor Inhibition 8.8 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: 1,4
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
epidermal growth factor receptor EGFR/EGFR Hs Inhibitor Inhibition 4.2
serine/threonine kinase 10 LOK/LOK(STK10) Hs Inhibitor Inhibition 20.3
ABL proto-oncogene 2, non-receptor tyrosine kinase Arg/ABL2(ARG) Hs Inhibitor Inhibition 33.0
EPH receptor A6 nd/EPHA6 Hs Inhibitor Inhibition 40.4
fms related receptor tyrosine kinase 3 Flt3/FLT3 Hs Inhibitor Inhibition 40.7
STE20 like kinase nd/SLK(STK2) Hs Inhibitor Inhibition 42.0
ret proto-oncogene Ret/RET Hs Inhibitor Inhibition 48.6
ABL proto-oncogene 1, non-receptor tyrosine kinase Abl/ABL1 Hs Inhibitor Inhibition 52.3
erb-b2 receptor tyrosine kinase 2 nd/ERBB2(HER2) Hs Inhibitor Inhibition 52.8
receptor interacting serine/threonine kinase 2 RIPK2/RIPK2 Hs Inhibitor Inhibition 57.9
Displaying the top 10 targets  View all targets in screen »