Therapeutically active compounds and their methods of use
Inventors
Assignees
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Publication Number
US-11865079-B2
Publication Date
2024-01-09
Expiration Date
Abstract
Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a purified compound described herein.
Core Innovation
The invention relates to cancer therapy driven by mutant isocitrate dehydrogenase 1 (IDH1) and/or mutant isocitrate dehydrogenase 2 (IDH2). Mutant IDH1 and mutant IDH2 are described as producing R(-)-2-hydroxyglutarate (2HG), which motivates inhibition of mutant IDH1 and/or mutant IDH2. The treatment focuses on mutant allele presence and cancer context driven by NADPH-dependent reduction of α-ketoglutarate to R(-)-2HG.
The invention provides specific substituted compounds (Compounds 1-7) with defined stereochemistry and functional groups, including purified forms and pharmaceutically acceptable salts. These compounds are described as inhibiting mutant IDH1 and/or mutant IDH2. The disclosure also frames R(-)-2HG as a target/biomarker related to mutant IDH activity in this context.
The document further describes treatment based on mutant IDH1/IDH2 status, including cancers with specific substitutions such as R132X for IDH1 and R140X/R172X for IDH2. It includes approaches that condition eligibility and therapeutic monitoring on 2HG measurement, including measurement by LC/MS and imaging biomarkers, and extends to analysis of R(-)-2HG derivatives.
Claims Coverage
The independent claims cover two inventive features: purified compound selection and pharmaceutical compositions with excipients.
Purified compound selected from Compounds 1-7
A compound selected from the enumerated options, or a pharmaceutically acceptable salt thereof, in purified form.
Pharmaceutical composition with excipients
A pharmaceutical composition comprising the claimed purified compound, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
The claim scope centers on purified embodiments of the specified substituted compounds, including pharmaceutically acceptable salts, and on pharmaceutical compositions that combine the claimed compounds or salts with pharmaceutically acceptable excipients.
Stated Advantages
Provides purified Compounds 1-7, or pharmaceutically acceptable salts thereof, for treating cancer characterized by IDH1 and/or IDH2 mutations.
Targets cancers including glioma and glioblastoma in the disclosed context.
Connects mutant IDH activity to R(-)-2-hydroxyglutarate (2HG) as a target/biomarker in the disclosed context.
Inhibit mutant IDH1 and/or mutant IDH2.
Documented Applications
Treating cancers characterized by IDH1 and/or IDH2 mutations, including glioma (low-grade and high-grade), glioblastoma, and other cancers explicitly listed in the document.
Conditioning eligibility and therapeutic monitoring on 2HG measurement, including LC/MS and imaging biomarkers.
Additional disease indications including Maffucci syndrome and Ollier disease.
Biologically active vorasidenib (AG-881) metabolites persisting after dosing.
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