Ligand id: 5677

Name: tofacitinib

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Structure and Physico-chemical Properties

2D Structure
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Calculated Physico-chemical Properties
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

Molecular properties generated using the CDK

Bioactivity Comments
Like many first generation kinase inhibitors tofacitinib exhibits a high degree of broad kinome selectivity but is in reality a pan-JAK-inhibitor. Additional kinases inhibited by tofacitinib in biochemical and cellular assays are described in [10]. Tofacitinib is also reported to exhibit immunosuppressive activity which prevents organ rejection in mice and primates [2].
Despite clinical efficacy in ulcerative colitis, tofacitinib did not show significant efficacy as an induction and maintenance therapy over placebo, in Crohn's disease patients (as evaluated in Phase 2 studies NCT01393626 and NCT01393899) [11].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 3 Hs Inhibitor Inhibition 6.7 – 9.0 pIC50 - 2-3,5,10
pIC50 8.2 (IC50 6x10-9 M) [10]
pIC50 6.7 – 9.0 (IC50 2.1x10-7 – 1x10-9 M) [2,5]
pIC50 7.3 (IC50 5.5x10-8 M) [3]
Description: In a biochemical enzyme assay.
Janus kinase 1 Hs Inhibitor Inhibition 7.8 pIC50 - 3
pIC50 7.8 (IC50 1.5x10-8 M) [3]
Description: In a biochemical enzyme assay.
Janus kinase 2 Hs Inhibitor Inhibition 7.1 pIC50 - 3
pIC50 7.1 (IC50 7.7x10-8 M) [3]
Description: In a biochemical enzyme assay.
protein kinase N1 Hs Inhibitor Inhibition 6.9 pIC50 - 10
pIC50 6.9 (IC50 1.22x10-7 M) [10]
tyrosine kinase 2 Hs Inhibitor Inhibition 6.3 pIC50 - 3
pIC50 6.3 (IC50 4.89x10-7 M) [3]
Description: In a biochemical enzyme assay.