The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
May. 15, 2018

Filed:

Jul. 16, 2015
Applicant:

Beth Israel Deaconess Medical Center, Inc., Boston, MA (US);

Inventors:

Kun Ping Lu, Newton, MA (US);

Xiao Zhen Zhou, Newton, MA (US);

Shuo Wei, Chestnut Hill, MA (US);

Assignee:
Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 31/203 (2006.01); A61K 45/06 (2006.01); A61K 31/122 (2006.01); A61K 31/192 (2006.01); A61K 31/428 (2006.01); A61K 31/353 (2006.01);
U.S. Cl.
CPC ...
A61K 31/203 (2013.01); A61K 31/122 (2013.01); A61K 31/192 (2013.01); A61K 31/353 (2013.01); A61K 31/428 (2013.01); A61K 45/06 (2013.01);
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.


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