Truncated ATF5, CEBPB, and CEBPD inhibitors for effective cancer treatment

This technology is a shortened version of cell-penetrating, dominant-negative peptides of ATF5, CEBPB, CEBPD for cancer treatment.

Unmet Need: Inhibitors of ATF5, CEBPB, CEBPD to suppress tumor proliferation

Activating transcription factor 5 (ATF5) is important for cancer cell survival and proliferation in a number of tumor types. ATF5 also associates with leucine zipper proteins, CEBPB and CEBPD, to regulate gene expression. However, there are currently no effective ATF5, CEBPB, or CEBPD inhibitors available.

The Technology: Short cell-penetrating effective inhibitors to suppress cancer survival

This technology describes truncated versions of cell-penetrating, dominant-negative peptides of human ATF5, CEBPB, CEBPD to suppress cancer survival. Shortened peptides allow greater mobility and penetration into tumors and demonstrate similar inhibitor effects as the full-length peptides. As such, this technology would be useful in cancer treatment.

Applications:

• Therapeutics for various cancers (glioblastoma, colon, breast, skin, etc.)
• Neurodegenerative disease treatments
• Treatment for diabetes, immune disorders, autoimmune diseases, and inflammatory diseases
• Tool for leucine zipper modulation research
• Dominant-negative peptide development

Advantages:

• Greater mobility into tumors
• Higher penetration into tumors
• Improved compound stability

Lead Inventor:

Lloyd Greene, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Zhou Q, Sun X, Pasquier N, Jefferson P, Nguyen TTT, Siegelin MD, Angelastro JM, Greene LA. “Cell-Penetrating CEBPB and CEBPD Leucine Zipper Decoys as Broadly Acting Anti-Cancer Agents” Cancers. 2021 May 20; 13(10): 2504.

• Sun X, Jefferson P, Zhou Q, Angelastro JM, Greene LA. “Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD” Mol Cancer Res. 2020 Feb; 18(2): 216-228.

• Sun X, Angelastro JM, Merino D, Zhou Q, Siegelin MD, Greene LA. “Dominant-negative ATF5 rapidly depletes survivin in tumor cells” Cell Death Dis. 2019 Sep 24; 10(10): 709.

• Karpel-Massler G, Horst BA, Shu C, Chau L, Tsujiuchi T, Bruce JN, Canoll P, Greene LA, Angelastro JM, Siegelin MD. “A Synthetic Cell-Penetrating Dominant-Negative ATF5 Peptide Exerts Anticancer Activity against a Broad Spectrum of Treatment-Resistant Cancers” Clin Cancer Res. 2016 Sep 15; 22(18): 4698-711.

• Cates CC, Arias AD, Nakayama Wong LS, Lamé MW, Sidorov M, Cayanan G, Rowland DJ, Fung J, Karpel-Massler G, Siegelin MD, Greene LA, Angelastro JM. “Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide” Oncotarget. 2016 Mar 15; 7(11): 12718-30.

Tech Ventures Reference:

• IR CU21274, CU22282, CU23024, CU23025

• Licensing Contact: Jerry Kokoshka