Methods and agents that stimulate mitochondrial turnover for treating disease
Inventors
Wang, Amy E. • Martorell-Riera, Alejandro • Gaffney, Kevin John
Assignees
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Publication Number
US-12343331-B2
Publication Date
2025-07-01
Expiration Date
Abstract
Provided herein are methods of stimulating mitophagy in a subject in need thereof administering to the subject a mitophagy-stimulating amount of a MAS receptor agonist or substance that triggers endogenous production of a MAS receptor agonist. The present disclosure also relates to medical intervention methods and agents, namely methods and agents for stimulation of mitochondrial turnover for treatment of disease in a mammal. The disclosure comprises a method of stimulating increased mitochondrial turnover in a mammal comprising administering to the mammal a pharmacologically suitable dose of a MAS receptor agonist; MAS receptor modulator; a substance that triggers endogenous production of a MAS receptor agonist; a substance that triggers endogenous production of a MAS receptor modulator; or any combination thereof. The pharmacological activity acting on MAS receptor in turn stimulates an increase in mitochondrial turnover in host cells, alleviating a disease state in the host mammalian organism.
Core Innovation
The disclosure provides mitophagy-stimulating heterocyclic non-peptidic angiotensin(1-7) mimetic compounds, including Compound 7 and related derivatives. It provides chemical structures and general structural definitions, including sulfonamide-imidazole derivatives linked through defined ring systems, and presents Compound 7 as a broader generic formula incorporating the defined ring system and substituent variability.
The structural definitions emphasize variability across multiple rings and substituent variables, including ring A, ring B, and ring C, with substituent variables R1-R5 and R6-R9, and additional variables A1-A4 and Z. The document further includes example substitution patterns, including trifluoromethoxy as R2, fluorinated aryl (F3CO), and pharmaceutically acceptable salt forms such as sodium salts, L-lysine salts, and tris(hydroxymethyl)aminomethane salts.
In the method context, Compound 7 is used as a MAS receptor agonist for treating a disease or condition in a subject in need thereof, where the disease or condition is selected from a long list of specified disorders or any combination thereof. The disclosure identifies below-normal mitochondrial turnover as a problem and links the MAS receptor agonist to mitophagy stimulation and associated mitochondrial turnover.
Claims Coverage
The independent claim coverage centers on treating a specified set of diseases or conditions by administering a mitophagy-stimulating amount of a MAS receptor agonist, with Compound 7 identified as the agonist in one claim set. Across the claims, the core inventive concept is treatment using MAS receptor agonist-driven mitophagy stimulation, with dependent claims adding mitochondrial biogenesis stimulation, human patient status, and administration as a pharmaceutical composition.
Treating disease by administering a mitophagy-stimulating mas receptor agonist compound 7
A method for treating a disease or condition in a subject in need thereof comprising administering to the subject a mitophagy-stimulating amount of a MAS receptor agonist, wherein the disease or condition is selected from the listed disorders or any combination, and wherein the MAS receptor agonist is Compound 7.
Adding an agent that stimulates mitochondrial biogenesis
The method further administers an effective amount of an agent that stimulates mitochondrial biogenesis.
Using a human patient as the subject
The method is performed with a human patient as the subject.
Administering the mas receptor agonist as a pharmaceutical composition
The MAS receptor agonist is administered as a pharmaceutical composition.
Overall, the claim coverage is directed to use of Compound 7 as a mitophagy-stimulating MAS receptor agonist for treating a defined list of diseases or conditions, with dependent refinements that add mitochondrial biogenesis stimulation, specify human patients, and limit administration to a pharmaceutical composition.
Stated Advantages
Stimulating increased mitochondrial turnover, including mitophagy.
Addressing disease or condition associated with below-normal mitochondrial turnover.
Documented Applications
Treating a disease or condition in a subject in need thereof by administering a mitophagy-stimulating MAS receptor agonist, including Compound 7, for the listed disorders or any combination thereof.
Inflammatory, neurodegenerative, and ocular diseases.
Mitochondrial DNA depletion syndromes and related disorders.
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