Compounds for the treatment of acute and chronic kidney disease
Inventors
Suto, Mark J. • Mathew, Bini • Agarwal, Anupam • Traylor, Amie M.
Assignees
UAB Research Foundation • Southern Research Institute • US Department of Veterans Affairs
Publication Number
US-11945781-B2
Publication Date
2024-04-02
Expiration Date
2041-11-17
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Abstract
The present disclosure is concerned with thioquinolinone compounds for the treatment of disorders associated with heme oxygenase-1 (HO-1) signaling dysfunction such as, for example, kidney diseases (e.g., chronic kidney disease, acute kidney injury). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Core Innovation
The invention relates to thioquinolinone compounds and compositions for use in the prevention and treatment of disorders associated with heme oxygenase-1 (HO-1) signaling dysfunction. Specifically, these compounds target kidney diseases such as chronic kidney disease and acute kidney injury. The disclosed compounds have defined chemical structures with various substituents that modulate HO-1 signaling.
The problem addressed by this invention is the significant morbidity and mortality associated with acute kidney injury (AKI) in hospitalized patients, with mortality rates as high as 80% in intensive care unit (ICU) patients. Current treatments, including renal replacement therapies and dialysis, have not substantially reduced this mortality. Moreover, AKI is linked to progression to chronic kidney disease (CKD). There remains a critical need for therapeutic compounds and methods to effectively treat kidney diseases associated with HO-1 signaling dysfunction.
Claims Coverage
The patent contains several independent claims covering novel compounds, pharmaceutical compositions, methods of treatment, methods of modifying HO-1 signaling, and kits. Four main inventive features are identified from these independent claims.
Compounds with specific thioquinolinone structures for treatment
Compounds selected from a defined group having a chemical structure with specific substitutions on the thioquinolinone core that modulate heme oxygenase-1 (HO-1) signaling dysfunction, particularly for kidney disease treatment.
Pharmaceutical compositions comprising the compounds
Pharmaceutical compositions comprising a therapeutically effective amount of the claimed compound and a pharmaceutically acceptable carrier suitable for administration to subjects in need.
Methods for treating disorders associated with HO-1 signaling dysfunction
Methods for treating HO-1 signaling dysfunction disorders in subjects by administering effective amounts of the claimed compounds, including treatment of kidney diseases such as chronic kidney disease and acute kidney injury, with considerations of prophylactic or therapeutic use and subject conditions.
Methods for modifying HO-1 signaling in subjects and cells
Methods for modifying or activating HO-1 signaling by administering or contacting subjects or cells with an effective amount of the claimed compounds, including validated assays for identifying compounds that modulate or increase HO-1 signaling.
The independent claims collectively cover novel thioquinolinone compounds, their pharmaceutical formulations, therapeutic methods for kidney diseases linked to HO-1 dysfunction, methods to modify HO-1 signaling in vivo and in cells, and associated kits, thereby providing an integrated approach to modulating HO-1 for treating related disorders.
Stated Advantages
Provides new compounds for treating kidney diseases associated with HO-1 signaling dysfunction where current therapies are inadequate.
Enables modulation of HO-1 signaling, potentially improving outcomes in acute and chronic kidney disease.
Includes validated assays for identifying compounds that modulate HO-1 signaling, facilitating drug discovery.
Documented Applications
Treatment of disorders associated with heme oxygenase-1 signaling dysfunction, specifically kidney diseases including chronic kidney disease and acute kidney injury.
Pharmaceutical use of thioquinolinone compounds for preventing and treating kidney diseases related to HO-1 signaling.
Methods for modifying HO-1 signaling in subjects and cells for therapeutic benefit.
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