compound 3a [Pipionne et al, 2018]   Click here for help

GtoPdb Ligand ID: 9965

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 3a was identified and optimised in a hit-to-lead study to identify inhibitors of the non-canonical NF-κB cascade in tumour cells [1]. 3a inhibits activity of the NF-κB-inducing kinase, NIK (MAP3K14), and is a representative example of a series of compounds with NIK selectivity, the most potent of which was 3e (biochemical IC50 2.9 μM).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 60.91
Molecular weight 283.03
XLogP 3.75
No. Lipinski's rules broken 0
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Canonical SMILES Cc1nn(c(c1c1ccc(c(c1)Cl)Cl)N)C(=O)C
Isomeric SMILES Cc1nn(c(c1c1ccc(c(c1)Cl)Cl)N)C(=O)C
InChI InChI=1S/C12H11Cl2N3O/c1-6-11(12(15)17(16-6)7(2)18)8-3-4-9(13)10(14)5-8/h3-5H,15H2,1-2H3
Bioactivity Comments
Compound 3a does not inhibit other components of the NF-κB pathway, IKKβ, IKKα or IKKε, or any of 44 kinases tested in a screening panel [1]. 3a is relatively metabolically unstable, a parameter that would need to be improved to warrant further clinical investigation.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase kinase kinase 14 Hs Inhibitor Inhibition 5.1 pIC50 - 1
pIC50 5.1 (IC50 8.4x10-6 M) [1]