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
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH et al.. (2003)
Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.
Science, 302 (5646): 875-8. [PMID:14593182]
3. Clark JD, Flanagan ME, Telliez JB. (2014)
Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.
J Med Chem, 57 (12): 5023-38. [PMID:24417533]
4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
5. Flanagan ME, Blumenkopf TA, Brissette WH, Brown MF, Casavant JM, Shang-Poa C, Doty JL, Elliott EA, Fisher MB, Hines M et al.. (2010)
Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection.
J Med Chem, 53 (24): 8468-84. [PMID:21105711]
6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
7. Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, Warner JD, Tanaka M, Steward-Tharp SM, Gadina M et al.. (2011)
Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550).
J Immunol, 186 (7): 4234-43. [PMID:21383241]
8. Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, Jabbari A, Winge MC et al.. (2016)
Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.
JCI Insight, 1 (15): e89776. [PMID:27699252]
9. Motoya S, Watanabe M, Kim HJ, Kim YH, Han DS, Yuasa H, Tabira J, Isogawa N, Arai S, Kawaguchi I et al.. (2018)
Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.
Intest Res, 16 (2): 233-245. [PMID:29743836]
10. Ostrovskyi D, Rumpf T, Eib J, Lumbroso A, Slynko I, Klaeger S, Heinzlmeir S, Forster M, Gehringer M, Pfaffenrot E et al.. (2016)
Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1).
Future Med Chem, 8 (13): 1537-51. [PMID:27572962]
11. Panés J, Sandborn WJ, Schreiber S, Sands BE, Vermeire S, D'Haens G, Panaccione R, Higgins PDR, Colombel JF, Feagan BG et al.. (2017)
Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.
Gut, 66 (6): 1049-1059. [PMID:28209624]
12. Panés J, Vermeire S, Lindsay JO, Sands BE, Su C, Friedman G, Zhang H, Yarlas A, Bayliss M, Maher S et al.. (2018)
Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies.
J Crohns Colitis, 12 (2): 145-156. [PMID:29028981]
13. Sandborn WJ, Su C, Sands BE, D'Haens GR, Vermeire S, Schreiber S, Danese S, Feagan BG, Reinisch W, Niezychowski W et al.. (2017)
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.
N Engl J Med, 376 (18): 1723-1736. [PMID:28467869]
14. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]