Substituted 3-amino-4-methylbenzenesulfonamides as small molecule inhibitors of ubiquitin-specific protease 28
Inventors
Buhrlage, Sara • Varca, Anthony • Hu, Bin
Assignees
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Publication Number
US-12668571-B2
Publication Date
2026-06-30
Expiration Date
Abstract
The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof and pharmaceutical composition comprising the compound of formula (I). The present composition also relates to methods treating a disease or disorder associated with ubiquitin-specific protease 28 (USP28), methods of treating cancer, and methods of inhibiting USP28.
Core Innovation
The invention discloses substituted 3-amino-4-methylbenzenesulfonamide compounds, including compounds of formula (I) and formula (II), and pharmaceutically acceptable salts thereof, characterized as USP28 inhibitors. The claims cover compounds of formula (I) having defined alternatives for X, R, and Z substituents with specified optional substitutions, alongside a separate selection of compounds whose specific structural list is not included in the provided text.
The disclosure describes pharmaceutical compositions and methods of treating a disease or disorder associated with USP28, specifically cancer. Supporting assessments include screening results across a 41-enzyme deubiquitinase panel, USP28 target engagement in K562 cells, and concentration-associated reductions in C-Myc and/or C-Myb across NOMO-1, K562, MOLM14, and MM1S cells to support USP28 engagement and cellular effects.
Claims Coverage
The provided claims identify three inventive features across independent claims 1, 19, and 20.
Compounds of formula (I)
Claim 1 covers a compound of formula (I), or a pharmaceutically acceptable salt thereof, with defined alternatives for the X, R, and Z substituents and specified optional substituents.
Selected compounds and pharmaceutically acceptable salts
Claim 19 covers a compound, or a pharmaceutically acceptable salt thereof, selected from a group of compounds not included in the provided claim text.
Treatment of a USP28-associated disease or disorder
Claim 20 covers a method of treating a disease or disorder associated with USP28 by administering to a subject in need thereof a compound, or a pharmaceutically acceptable salt thereof, selected from a group not included in the provided claim text, with cancer identified in a dependent claim.
The independent claims cover a structurally defined compound genus of formula (I), a selection of compounds whose list is not included in the provided claim text, and a method of treating a USP28-associated disease or disorder.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of a disease or disorder associated with ubiquitin-specific protease 28 (USP28), including cancer, using a claimed compound or pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a claimed compound and a pharmaceutically acceptable carrier.
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