Methods and compositions for the inhibition of PIN1
Inventors
Lu, Kun Ping • Boxer, Matthew Brian • Davis, Mindy Irene Emily • Pragani, Rajan • Shen, Min • Simeonov, Anton Momtchilov • Wei, Shuo • Zhou, Xiao Zhen
Assignees
Beth Israel Deaconess Medical Center Inc • US Department of Health and Human Services • Office of Technology Transfer
Publication Number
US-11129835-B2
Publication Date
2021-09-28
Expiration Date
2033-06-07
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.
Core Innovation
The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels using compounds defined herein, specifically identified as Table 1 Compounds. It provides a method of contacting Pin1 protein, which can be within human cells, with these compounds in therapeutically effective amounts for treating immune disorders or proliferative disorders.
The invention also includes diagnostic and prognostic methods involving the determination of Pin1 marker expression levels in subjects prior to or after treatment, which can influence or evaluate the administration of Table 1 Compounds. Pin1 marker levels can be assessed from biological samples such as blood, urine, biopsies, saliva, and others. The invention highlights reduced Ser71 phosphorylation of Pin1 as an embodiment of a Pin1 marker used to select patients for treatment.
The problem addressed arises from the elevated Pin1 activity associated with immune disorders and proliferative disorders, including many cancers with poor prognosis. Existing treatments for immune disorders rely on immunosuppressive agents that vary in efficacy and often have adverse effects. Similarly, cancer detection and treatment methods are limited, and understanding the multiple gene products such as Pin1 involved in tumor development is essential. Pin1 overexpression activates numerous oncogenes and inactivates tumor suppressors, contributing to tumorigenesis, hence the need for specific Pin1 inhibitors.
Claims Coverage
The patent contains one independent claim detailing a method of inhibiting Pin1 with specific compounds.
Use of compounds with defined chemical structures to inhibit Pin1
A method of inhibiting Pin1 by contacting it with a compound having a specific chemical structure defined by formula in the claims, including stereoisomers and pharmaceutically acceptable salts.
Use of selected compounds from a defined subset
The use of compounds selected specifically from compounds numbered 28 to 32 for inhibiting Pin1.
Inhibition of Pin1 located in cells
The method includes inhibition of Pin1 when present inside cells, including specifically human cells.
The independent claim centers on the method of inhibiting cellular Pin1 using specified compounds with defined structures, focusing on chemically characterized inhibitors effective in human cells.
Stated Advantages
Pin1 inhibitors can suppress numerous oncogenic pathways simultaneously, useful for treating aggressive and/or drug-resistant cancers.
Pin1 inhibitors offer a novel therapeutic approach that selectively inhibits type I IFN response while leaving proinflammatory cytokine production unaffected.
Combination therapies with Table 1 Compounds can reduce the doses of other therapeutic agents, potentially minimizing adverse side effects.
Documented Applications
Treatment of immune disorders characterized by elevated Pin1 levels, including a wide range of diseases such as multiple sclerosis, Crohn's disease, asthma, lupus, rheumatoid arthritis, psoriasis, and others expressly listed.
Treatment of proliferative disorders, including a variety of leukemias, lymphomas, sarcomas, carcinomas, and specific cancers such as breast, pancreatic, ovarian, prostate, lung, bladder, and brain cancers among others explicitly identified.
Use in combination therapy with other anti-inflammatory, anti-microbial, anti-viral, and anti-cancer agents to enhance efficacy and reduce toxicity.
Diagnostic and prognostic uses involving measuring Pin1 marker levels in diverse biological samples to select or monitor subjects for treatment with Pin1 inhibitors.
Interested in licensing this patent?