Compositions and methods for inhibiting IDO1
Inventors
Hamrick, Mark • Isales, Carlos • Lebedyeva, Iryna
Assignees
Augusta University • Augusta University Research Institute Inc
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Publication Number
US-11858908-B2
Publication Date
2024-01-02
Expiration Date
Abstract
Provided herein are compounds that inhibit IDO1 and methods of use thereof. Also provided are pharmaceutical compositions and medicaments that include the compounds described herein as well as methods of treating sarcopenia or age-related muscle loss.
Core Innovation
The disclosure relates to small-molecule IDO1 inhibitors and antagonists linked to IDO1 targeting in the kynurenine pathway, involving tryptophan conversion to kynurenine (KYN). The compounds are defined by structural formulas, including Formula Ia, Ib, Ic, I, IIa, and IIb, and the disclosure addresses stereoisomers, pharmaceutically acceptable salts, prodrugs, zwitterion, solvate, and polymorph forms.
The invention further includes pharmaceutical compositions containing the described IDO1 inhibitors and antagonists. The disclosure recites methods that include inhibiting IDO1 and reducing kynurenine production, and these methods are framed as being for treating IDO1-related disorders, including sarcopenia, skeletal muscle mass loss, age-related muscle loss, cachexia, and muscle wasting.
Representative compound structures are shown in images and files and are used to specify particular compound structures corresponding to the claimed chemical structures. The disclosure also includes specific ionic and salt examples, including rosmarinic acid carnitine, rosmarinic acid creatine, rosmarinic acid nicotinic acid, and rosmarinic acid metformin salts.
Claims Coverage
The identified claim coverage is centered on structurally defined compounds, with dependent claims refining that structure using attached structure images, files, identifiers, and explicit component labels. In total, the inventive features focus on the chemical structure of the IDO1 inhibitor and antagonist compounds.
Structurally defined compound structure
A compound having the structure defined in the claim, where the compound is specified by a chemical structure as represented by the provided structural definitions or images.
Compound structure specified by structural images and files
The compound is specified as having the chemical structure shown in provided structural images or attached structure files, identified by the document’s structural-image identifiers.
Compound structure specified with explicit chemical component labels
The compound is specified with explicit chemical group or component labels in connection with a structure identifier, defining the compound’s structure by the labeled groups shown with the referenced structure identifier.
Across the identified claims, the inventive coverage is primarily structural: the claimed compounds are defined by chemical structure, and dependent claims further restrict the scope by reference to specific structure images, files, identifiers, and labeled components.
Stated Advantages
Treating sarcopenia and skeletal muscle mass loss.
Treating cachexia.
Treating age-related muscle loss and muscle wasting.
Inhibiting IDO1 and reducing kynurenine production and downstream tryptophan metabolite levels.
Reported reduction of kynurenine levels by more than 50% versus IFN-gamma alone for certain test compounds.
Assay correlation reported between ELISA and LC/MS.
Documented Applications
Therapeutic treatment of sarcopenia and skeletal muscle mass loss.
Therapeutic treatment of cachexia.
Therapeutic treatment of age-related muscle loss and muscle wasting.
Inhibition of IDO1/kynurenine pathway activity by reducing kynurenine production and downstream tryptophan metabolite levels.
Use in combination therapy and via pharmaceutical compositions with multiple administration routes including parenteral, oral, enteral, topical, mucosal, and transdermal administration.
Use of virtual screening and assay evaluation and molecular docking studies in support of inhibiting IDO1/kynurenine pathways.
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