JAK3 inhibitor 34   Click here for help

GtoPdb Ligand ID: 10157

Synonyms: compound 34 [PMID: 30423248]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 34 is an exemplar selective and covalent Janus kinase 3 (JAK3) inhibitor that was discovered by Casimiro-Garcia et al. [1]. It was designed such that its cyanamide group directly engages the Cys909 residue in JAK3.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 77.39
Molecular weight 351.15
XLogP 4.39
No. Lipinski's rules broken 0
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Canonical SMILES N#CNC1CCc2c1cc(cc2)c1ncnc2c1c(c[nH]2)c1ccccc1
Isomeric SMILES N#CN[C@H]1CCc2c1cc(cc2)c1ncnc2c1c(c[nH]2)c1ccccc1
InChI InChI=1S/C22H17N5/c23-12-25-19-9-8-15-6-7-16(10-17(15)19)21-20-18(14-4-2-1-3-5-14)11-24-22(20)27-13-26-21/h1-7,10-11,13,19,25H,8-9H2,(H,24,26,27)/t19-/m0/s1
Bioactivity Comments
Inhibitor 34 exhibits ~70-fold selectivity for JAK3 compared JAK1, and greater for the other JAK subfamily members [1]. Mechanistically compound 34 mediates a reduction in IL-15 induced STAT5 phosphorylation via the JAK1/JAK3 heterodimer (IC50 458 nM in PBMCs), but has no effect on IL-10 mediated STAT3 phosphorylation via the JAK1/TYK2 heterodimer, which confirms the JAK3 specificity of the compound.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 3 Primary target of this compound Hs Inhibitor Inhibition 7.3 pIC50 - 1
pIC50 7.3 (IC50 4.9x10-8 M) [1]
Janus kinase 1 Hs Inhibitor Inhibition 5.5 pIC50 - 1
pIC50 5.5 (IC50 3.345x10-6 M) [1]
Janus kinase 2 Hs Inhibitor Inhibition <5.2 pIC50 - 1
pIC50 <5.2 (IC50 >6.578x10-6 M) [1]
tyrosine kinase 2 Hs Inhibitor Inhibition <5.0 pIC50 - 1
pIC50 <5.0 (IC50 >1x10-5 M) [1]