tofacitinib   Click here for help

GtoPdb Ligand ID: 5677

Synonyms: CP-690,550 | CP-690550 | tasocitinib | Xeljanz®
Approved drug PDB Ligand Immunopharmacology Ligand
tofacitinib is an approved drug (FDA (2012), EMA (2017))
Compound class: Synthetic organic
Comment: Tofacitinib is an orally active, Type-1 Janus kinase (JAK) inhibitor and it was first approved by the US FDA in 2012. Tofacitinib was originally described as a selective JAK3 inhibitor [2], but subsequent analysis has revealed it to be a pan-JAK inhibitor, with predominant JAK1 inhibition [3,5].
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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

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View more information in the IUPHAR Pharmacology Education Project: tofacitinib

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 6
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 88.91
Molecular weight 312.17
XLogP 1.34
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 N#CCC(=O)N1CCC(C(C1)N(c1ncnc2c1cc[nH]2)C)C
Isomeric SMILES N#CCC(=O)N1CC[C@H]([C@H](C1)N(c1ncnc2c1cc[nH]2)C)C
InChI InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1
InChI Key UJLAWZDWDVHWOW-YPMHNXCESA-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: 4,14
Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
Janus kinase 3 JAK3(JH1domain-catalytic) Hs Inhibitor Inhibition 9.8 pKd
Janus kinase 2 JAK2(JH1domain-catalytic) Hs Inhibitor Inhibition 9.2 pKd
Janus kinase 1 JAK1(JH1domain-catalytic) Hs Inhibitor Inhibition 8.8 pKd
tyrosine kinase 2 TYK2(JH1domain-catalytic) Hs Inhibitor Inhibition 8.3 pKd
doublecortin like kinase 3 DCAMKL3 Hs Inhibitor Inhibition 7.9 pKd
tyrosine kinase non receptor 1 TNK1 Hs Inhibitor Inhibition 6.9 pKd
protein kinase N1 PKN1 Hs Inhibitor Inhibition 6.8 pKd
NUAK family, SNF1-like kinase, 2 SNARK Hs Inhibitor Inhibition 6.6 pKd
Rho associated coiled-coil containing protein kinase 2 ROCK2 Hs Inhibitor Inhibition 6.4 pKd
LCK proto-oncogene, Src family tyrosine kinase LCK Hs Inhibitor Inhibition 6.3 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: 1,6
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
Janus kinase 3 JAK3/JAK3 Hs Inhibitor Inhibition 1.9
Janus kinase 1 nd/JAK1 Hs Inhibitor Inhibition 2.3
Janus kinase 2 JAK2/JAK2 Hs Inhibitor Inhibition 5.1
tyrosine kinase 2 nd/TYK2 Hs Inhibitor Inhibition 12.0
protein kinase N1 nd/PKN1(PRK1) Hs Inhibitor Inhibition 16.5
leucine rich repeat kinase 2 nd/LRRK2 Hs Inhibitor Inhibition 51.3
EPH receptor B3 EphB3/EPHB3 Hs Inhibitor Inhibition 54.9
megakaryocyte-associated tyrosine kinase nd/CTK(MATK) Hs Inhibitor Inhibition 66.9
Rho associated coiled-coil containing protein kinase 2 ROCK-II/ROCK2 Hs Inhibitor Inhibition 69.9
NUAK family kinase 1 ARK5/ARK5(NUAK1) Hs Inhibitor Inhibition 71.2
Displaying the top 10 targets  View all targets in screen »