Methods and compositions for inhibiting neddylation of proteins
Patent Number: US9447156
Executive Summary:
General Description:
Like ubiquitin, neuronal precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently attached to target proteins in a process termed neddylation. Like ubiquitination, neddylation is dependent on the E2 conjugating enzyme UBE2M and on the E3 ligase DCN1. DCN1 gene is reportedly amplified in most squamous cell carcinomas. The main substrate of NEDD8 is the Cullin family of proteins, which reportedly play a role in in DNA damage repair and cell cycle regulation.
Invention US9447156 describes a novel binding pocket on UBE2M along with small molecule/peptides that can bind to it. Blocking this pocket would inhibit neddylation compromising DNA repair pathways in cancerous cells.
Strengths:
Weaknesses:
Patent Status:
Inventor Bio: Brenda A. Schulman
https://www.stjude.org/directory/s/brenda-schulman.html
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Issued on 2016-09-20
- Patent Link: https://patents.google.com/patent/US9447156/
- Research Institute: St. Jude Children's Research Hospital
- Disease Focus: Cancer
- Basis of Invention: Inhibition of NEDD8 activity by inhibiting the binding of NEDD8 E2 enzymes using small molecules and peptides
- How it works: Neuronal precursor cell expressed developmentally downregulated protein 8 (NEDD8) is a ubiquitin like protein and modifies proteins involved in DNA damage repair, cell proliferation and inflammation. In order to modify proteins, NEDD8 requires the activity of E2 enzymes. Blocking of a binding pocket on the E2 enzyme would inhibit its activity and consequently prevent NEDD8 mediated modifications and inhibit cell growth
- Lead Challenge Inventor: Brenda A. Schulman
- Inventors: Julie K. Monda, Brenda A. Schulman and Daniel C. Scott
- Development Stage: Lead optimization – in vitro data only
- Novelty:
- Disruption of neddylation via its E2 enzyme
- Clinical Applications:
- Treatment of cancer
- Treatment of inflammatory disorders
- Treatment of cancer
General Description:
Like ubiquitin, neuronal precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently attached to target proteins in a process termed neddylation. Like ubiquitination, neddylation is dependent on the E2 conjugating enzyme UBE2M and on the E3 ligase DCN1. DCN1 gene is reportedly amplified in most squamous cell carcinomas. The main substrate of NEDD8 is the Cullin family of proteins, which reportedly play a role in in DNA damage repair and cell cycle regulation.
Invention US9447156 describes a novel binding pocket on UBE2M along with small molecule/peptides that can bind to it. Blocking this pocket would inhibit neddylation compromising DNA repair pathways in cancerous cells.
Strengths:
- Peptides that target the E2 enzyme are novel
- Identification of E2 binding pockets provides a new target for screens to conducted against
Weaknesses:
- No in vivo data
Patent Status:
- Priority date: 2011-05-17
- Filing date: 2012-05-16
- Publication date: 2016-09-20
- Grant date: 2016-09-20
Inventor Bio: Brenda A. Schulman
https://www.stjude.org/directory/s/brenda-schulman.html
