compound 29 [Moslin et al., 2017]   Click here for help

GtoPdb Ligand ID: 9992

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 29 binds to the JH2 pseudokinase domain of the Janus kinase family enzyme, TYK2 [1].
Various cytokines and their receptors mediate intracellular signalling through pairs of Janus kinase family enzymes. TYK2 dimerises with JAK2 to mediate IL-12 and IL-23 signalling (both are p40 subunit containing cytokines), and with JAK1 for the IFNα/β pathway. Both of these TYK2-dependent pathways are validated as druggable targets for the development of pharmaceuticals for the treatment of autoimmune diseases. Displacement of the ATP that binds to the JH2 pseudokinase domain allosterically disrupts TYK2 catalytic activity, in a mechanism that appears to stablise the kinase in an auto-inhibitory conformation. Expolting this domain is being investigated with the aim of identifying inhibitors with improved selectivity compared to traditional orthosteric JH1 domain ATP-competitive inhibitors.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 5
Rotatable bonds 10
Topological polar surface area 133.04
Molecular weight 450.18
XLogP 1.49
No. Lipinski's rules broken 0
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Canonical SMILES COc1c(cc(cc1F)F)Nc1cc(NC)c2n(n1)c(cn2)C(=O)NCCC(CO)(O)C
Isomeric SMILES COc1c(cc(cc1F)F)Nc1cc(NC)c2n(n1)c(cn2)C(=O)NCCC(CO)(O)C
InChI InChI=1S/C20H24F2N6O4/c1-20(31,10-29)4-5-24-19(30)15-9-25-18-14(23-2)8-16(27-28(15)18)26-13-7-11(21)6-12(22)17(13)32-3/h6-9,23,29,31H,4-5,10H2,1-3H3,(H,24,30)(H,26,27)
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Molecular structure representations generated using Open Babel