brensocatib   Click here for help

GtoPdb Ligand ID: 9412

Synonyms: AZD7986 | compound 30 [1] | INS 1007 | INS1007
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Brensocatib (formerly AZD7986) is reported as a second generation, oral, selective and reversible inhibitor of dipeptidyl peptidase 1 (DPP1; a.k.a. cathepsin C) [1]. Cathepsin C is required for the activation of proinflammatory neutrophil serine proteases, making this enzyme a drug target whose pharmacological inhibition has potential in the treatment of diseases such as chronic obstructive pulmonary disease (COPD) which is driven in part by excessive neutrophil activation and dysregulated neutrophil elastase activity. The compound was originally developed by AstraZeneca, but is now being progressed by Insmed.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 109.29
Molecular weight 420.18
XLogP 2
No. Lipinski's rules broken 0
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Canonical SMILES N#CC(Cc1ccc(cc1)c1ccc2c(c1)n(C)c(=O)o2)NC(=O)C1CNCCCO1
Isomeric SMILES N#C[C@H](Cc1ccc(cc1)c1ccc2c(c1)n(C)c(=O)o2)NC(=O)[C@@H]1CNCCCO1
InChI InChI=1S/C23H24N4O4/c1-27-19-12-17(7-8-20(19)31-23(27)29)16-5-3-15(4-6-16)11-18(13-24)26-22(28)21-14-25-9-2-10-30-21/h3-8,12,18,21,25H,2,9-11,14H2,1H3,(H,26,28)/t18-,21-/m0/s1
Bioactivity Comments
AZD7986 has a half-life of >10 hours in plasma, does not bind to aortic tissue in vitro or in vivo (aortic binding being a liability of previously reported cathepsin C inhibitors), and is selective over other human recombinant cathepsins, other enzymes, receptors, ion channels, and transporters tested [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
cathepsin C Primary target of this compound Hs Inhibitor Inhibition 8.6 pKd - 1
pKd 8.6 (Kd 2.5x10-9 M) [1]
Description: Surface plasmon resonance direct binding assay
cathepsin C Primary target of this compound Hs Inhibitor Inhibition 8.4 pIC50 - 1
pIC50 8.4 (IC50 3.98x10-9 M) [1]
Description: In vitro enzyme assay
cathepsin C Rn Inhibitor Inhibition 7.7 pIC50 - 1
pIC50 7.7 (IC50 1.99x10-8 M) [1]
Description: In vitro enzyme assay
cathepsin C Mm Inhibitor Inhibition 7.6 pIC50 - 1
pIC50 7.6 (IC50 2.51x10-8 M) [1]
Description: In vitro enzyme assay