Method of treating cancer with modulators of SCFSkp2
Patent Number: US9261497
Executive Summary:
General Description:
The Skp1-Cullin1-F-box (“SCF”) family is a multi-protein RING-finger E3 ligase that drives each stage of the cell cycle by controlling the protein levels of cyclins and cyclin-dependent kinase inhibitors (“CKI”s). The F-box protein S-phase kinase-associated protein 2 (“Skp2”) is overexpressed in human cancers and implicated in multiple murine models. High-throughput screens designed to detect small molecules that stabilize p27 identified compounds that either inhibited 26S proteasome activity, prevented Skp2 from incorporating into the SCF complex, or downregulated Skp2 mRNA, hence, resulting in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. However, no inhibitors specifically and directly targeted to the E3 ligase activity of Skp2 have been identified. The present invention is directed to overcoming this issue.
Strengths:
Weaknesses:
Patent Status:
Inventor Bio: Michele Pagano
https://med.nyu.edu/faculty/michele-pagano
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Issued (Grant date: 2016-02-16)
- Patent Link: https://patents.google.com/patent/US9261497/
- Research Institute: New York University
- Disease Focus: Cancers or disorders associated with SCF-Skp2 activity, including endometrial cancer, multiple myeloma, mantle cell lymphoma, and breast cancer
- Basis of Invention: Preventing Skp2 from incorporating into the SCF complex results in cell-cycle arrest and activation of autophagy in cancer cells
- How it works: This inhibitor specifically and directly blocks the E3 ligase activity of Skp2
- Lead Challenge Inventor: Michele Pagano
- Inventors: Cardozo; Timothy (New York, NY), Pagano; Michele (New York, NY), Wu; Lily (Freeport, NY), Gold; Leslie I. (New York, NY)
- Development Stage: in vitro
- Novelty: No inhibitors specifically and directly targeted to the E3 ligase activity of Skp2 have been identified
- Clinical Applications: Treatment of cancer cases where patients benefits from this type of inhibitor
General Description:
The Skp1-Cullin1-F-box (“SCF”) family is a multi-protein RING-finger E3 ligase that drives each stage of the cell cycle by controlling the protein levels of cyclins and cyclin-dependent kinase inhibitors (“CKI”s). The F-box protein S-phase kinase-associated protein 2 (“Skp2”) is overexpressed in human cancers and implicated in multiple murine models. High-throughput screens designed to detect small molecules that stabilize p27 identified compounds that either inhibited 26S proteasome activity, prevented Skp2 from incorporating into the SCF complex, or downregulated Skp2 mRNA, hence, resulting in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. However, no inhibitors specifically and directly targeted to the E3 ligase activity of Skp2 have been identified. The present invention is directed to overcoming this issue.
Strengths:
- A novel approach that can be used to treat cancer as part of a personalized medicine initiative
Weaknesses:
- Has not been tested in animal models and clinical trials
Patent Status:
- Priority date: 2012-10-16
- Filing date: 2013-10-16
- Publication date: 2016-02-16
- Grant date: 2016-02-16
Inventor Bio: Michele Pagano
https://med.nyu.edu/faculty/michele-pagano
