GtoPdb Ligand ID: 9432

Synonyms: compound 2 [PMID: 27983835] | PF 0626327 | PF0626327
Compound class: Synthetic organic
Comment: PF-06263276 is a pan-JAK inhibitor [1]. There are two E/Z isomers as PubChem CID 122196621 and PubChem CID 71495793 but these are not resolved in the publication.
2D Structure
Click here for structure editor
Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 126.92
Molecular weight 566.26
XLogP 5.55
No. Lipinski's rules broken 1
Canonical SMILES CCc1cc(O)c(cc1c1ccc2c(c1)[nH]nc2c1nc2c([nH]1)CCN(C2)C(=O)c1cnc(cn1)N1CCCCC1)F
Isomeric SMILES CCc1cc(O)c(cc1c1ccc2c(c1)[nH]nc2c1nc2c([nH]1)CCN(C2)C(=O)c1cnc(cn1)N1CCCCC1)F
InChI InChI=1S/C31H31FN8O2/c1-2-18-13-27(41)22(32)14-21(18)19-6-7-20-24(12-19)37-38-29(20)30-35-23-8-11-40(17-26(23)36-30)31(42)25-15-34-28(16-33-25)39-9-4-3-5-10-39/h6-7,12-16,41H,2-5,8-11,17H2,1H3,(H,35,36)(H,37,38)
Bioactivity Comments
In vitro and in vivo potencies, and the pharmacokinetic and safety profiles of PF-06263276 indicate suitability for inhaled or topical therapy to treat inflammatory diseases, such as COPD or psoriasis, through direct administration to the lungs or skin, thus avoiding any systemic effects of JAK inhibition [1]. IC50 evaluation was performed at 100nM ATP.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 1 Hs Inhibitor Inhibition 8.7 pIC50 - 1
pIC50 8.7 (IC50 2.2x10-9 M) [1]
Janus kinase 2 Hs Inhibitor Inhibition 7.6 pIC50 - 1
pIC50 7.6 (IC50 2.31x10-8 M) [1]
tyrosine kinase 2 Hs Inhibitor Inhibition 7.5 pIC50 - 1
pIC50 7.5 (IC50 2.97x10-8 M) [1]
Janus kinase 3 Hs Inhibitor Inhibition 7.2 pIC50 - 1
pIC50 7.2 (IC50 5.99x10-8 M) [1]