- SMALL-MOLECULE NADPH OXIDASE 2 INHIBITORS
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The invention provides compounds of Formula (II) which comprise two terminal 2-aminoquinoline moieties. They are novel and potent inhibitors of the p47phox-p22phox protein-protein interaction that can inhibit the assembly and thus activation of the multisubunit and superoxide-generating NADPH oxidase 2 complex. The compounds are therapeutically relevant as they can reduce cell damage in diseases where NADPH oxidase 2 is a major contributor to generation of reactive oxygen species (ROS) and oxidative stress.
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Page/Page column 115; 120; 150-151
(2021/06/04)
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- ISOQUINOLINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to a compound suitable for use as a kinase inhibitor
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Page/Page column 181-183
(2021/02/12)
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- Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery
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Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
- Solbak, Sara Marie ?ie,Zang, Jie,Narayanan, Dilip,H?j, Lars Jakobsen,Bucciarelli, Saskia,Softley, Charlotte,Meier, Sebastian,Langkilde, Annette Eva,Gotfredsen, Charlotte Held,Sattler, Michael,Bach, Anders
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p. 1156 - 1177
(2020/03/10)
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- QUINAZOLINE-PYRIDINE DERIVATIVES FOR THE TREATMENT OF CANCER-RELATED DISORDERS
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Compounds that inhibit at least one of the A2A and A2B adenosine receptors, and compositions containing the compound and methods for synthesizing the compound, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by the adenosine A2A receptor and/or the adenosine A2B receptor.
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Paragraph 0311
(2018/11/26)
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- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
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