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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key AEXFXNFMSAAELR-RXVVDRJESA-N
No information available.
Summary of Clinical Use Click here for help
Brensocatib (formerly AZD7986) has completed Phase 1 clinical trials in healthy volunteers (see NCT02303574 and NCT02653872) which confirm on-target effects [2]. Insmed are progressing AZD7986 (re-assigned as INS1007) as an anti-inflammatory approach to treat the cycle of inflammation, infection, and debilitating lung damage that is associated with non-cystic fibrosis bronchiectasis (NCFBE).

SARS-CoV-2 and COVID-19: Plans are underway to examine the potential of INS1007 to treat COVID-19-related acute respiratory distress syndrome (ARDS), in the UK STOP-COVID19 clinical trial which is being led from the University of Dundee. The INS1007 arm of the study aims to administer the drug to 150 COVID-19 patients (plus 150 in the placebo arm) across 10 UK hospitals.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Cathepsin C cleaves the N-terminal dipeptide of neutrophil serine proteases (NSPs) during neutrophil maturation in the bone marrow. This action leads to neutrophils without stored activated NSPs (e.g. neutrophil elastase, proteinase 3, and cathepsin G). In neutrophil-driven lung disease, treatment with cathepsin C inhibitors should reduce availability of the active NSPs that cause inflammatory lung damage, leading to improvement of disease symptoms.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02653872 A Phase I Study to Assess PK of AZD7986 Alone & With Verapamil, Itraconazole or Diltiazem in Healthy Subjects Phase 1 Interventional AstraZeneca
NCT02303574 Single + Multiple Ascending Dose and Food Effect Study of AZD7986 in Healthy Volunteers, PK, PD and Safety Study Phase 1 Interventional AstraZeneca
NCT03218917 Assessment of INS1007 in Subjects With Non-Cystic Fibrosis Bronchiectasis Phase 2 Interventional Insmed Incorporated This trial has been completed, but as of April 2020 no results have been published. The Insmed website indicates that they are planning to progress INS1007 to Phase 3 in bronchiectasis following positive top-line results from this study.