ATRA for modulating Pin1 activity and stability
US9968579B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jul 16, 2015 |
| Grant date | May 15, 2018 |
| Priority date | — |
| Expiry date | Jul 16, 2035 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61P37/02
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations. ATRA-containing formulations may be used in combinations with other existing therapies including chemotherapy or molecularly targeted drugs and other standard of care.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.