Compounds and uses thereof
Inventors
Ruppel, Sabine K. • Yang, Zhaoxia • LOWE, Jason T. • Voigt, Johannes H.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12528825-B2
Publication Date
2026-01-20
Expiration Date
Abstract
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
Core Innovation
The invention relates to a compound having a defined chemical structure and to pharmaceutically acceptable salt forms of that compound, including specific formic acid salt forms designated as D1-A Formic Acid, D1-C Formic Acid, and D1-D Formic Acid. The disclosure also includes stereodefined intermediates, stereoisomer preparation, and thienopyridine-based intermediates and final drug-like compounds, including stereoisomeric forms and formate salts.
The disclosed compound is presented as a BRD9 degrader, and proteomics is described using affinity purification and mass spectrometry to identify BRD9 as an interacting component of SS18-SSX-containing BAF complexes. Biological evaluation includes a SYO-1 BRD9 NanoLuc cell-based degradation assay and synovial sarcoma cell line assays showing selective growth inhibition and pro-apoptotic effects versus non-synovial control cancer lines.
The disclosed results report sub-1 µM IC50 values for BRD9 degradation for diastereomer mixtures of D1, with additional in vivo synovial sarcoma tumor studies reporting tumor growth inhibition and complete BRD9 degradation in tumors up to 168 hours post-dose.
Claims Coverage
The partial claim set includes two independent claims covering a compound with a specified chemical structure, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising that compound, or salt, and a pharmaceutically acceptable excipient. Across dependent claims, the principal claim coverage is shifted to methods of treatment for SS18-SSX fusion protein-related disorders, BRD9-related disorders, and cancer, including extensive selection of named cancer types and sarcoma subtypes.
Specified compound structure with salts
A compound having the structure of the claimed chemical formula, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition with pharmaceutically acceptable excipient
A pharmaceutical composition comprising the compound of the specified structure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
Treatment of SS18-SSX fusion protein-related disorder
A method for treating an SS18-SSX fusion protein-related disorder in a subject by administering an effective amount of the compound of the specified structure, or a pharmaceutically acceptable salt.
Treatment of BRD9-related disorder
A method for treating a BRD9-related disorder by administering an effective amount of the compound of the specified structure, or a pharmaceutically acceptable salt, to a subject in need.
Treatment of cancer
A method for treating cancer in a subject by administering an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt thereof.
Cancer type selection including specified malignancies and lung cancer types
A method of treating cancer where the cancer is one of the listed types including malignant rhabdoid tumor, CD8+ T-cell lymphoma, and various specified carcinomas and lung cancer types.
Sarcoma subtype selection including soft tissue sarcoma and numerous named sarcoma entities
A method where the sarcoma is selected from the listed sarcoma subtypes, including soft tissue sarcoma and numerous named sarcoma entities.
Claim coverage primarily protects the specified D1 chemical structure as a compound, its pharmaceutically acceptable salt forms, and a corresponding pharmaceutical composition including that compound plus an excipient. Dependent claims further narrow use to treating SS18-SSX fusion protein-related disorders, BRD9-related disorders, and defined subsets of cancer with named cancer types and sarcoma subtypes.
Stated Advantages
Sub-1 µM IC50 values for BRD9 degradation for diastereomer mixtures of D1 in a SYO-1 BRD9 NanoLuc cell-based degradation assay.
Tumor growth inhibition in a synovial sarcoma tumor model.
Complete BRD9 degradation in tumors up to 168 hours post-dose.
Selective growth inhibition and pro-apoptotic effects in synovial sarcoma cell lines versus non-synovial control cancer lines.
Documented Applications
BRD9 degrader application evaluated in a SYO-1 BRD9 NanoLuc cell-based degradation assay, including reported sub-1 µM IC50 values for BRD9 degradation for diastereomer mixtures of D1.
In vivo synovial sarcoma tumor model application, including tumor growth inhibition and complete BRD9 degradation in tumors up to 168 hours post-dose.
Cell-based assays in synovial sarcoma cell lines showing selective growth inhibition and pro-apoptotic effects of BRD9 degrader/binder compounds versus non-synovial control cancer lines, including apoptosis and cellular proliferation readouts.
Proteomics using affinity purification and mass spectrometry to identify BRD9 as an interacting component of SS18-SSX-containing BAF complexes.
Synthetic chemistry for preparing thienopyridine-based intermediates and final drug-like compounds, including stereoisomeric forms and formate salts.
Interested in licensing this patent?