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Novel and Highly Specific Anti-Cancer Peptide Drug Derived From NAF-1

Nechushtai Rachel, HUJI, Faculty of Science, The Alexander Silberman Institute for Life Sciences
FRIEDLER Assaf, HUJI, Faculty of Science, The Institute of Chemistry

Keywords

Cancer, Peptide, NAF-1

Current development stage

Initial in-vivo studies completed

Application

It was recently shown that enhanced expression of NAF-1, is associated with different cancers, including breast, prostate, gastric, cervical, liver, and laryngeal. Silencing of NAF-1 expression in breast, or gastric, cancer cells significantly inhibited cellular proliferation and tumorigenicity, whereas overexpression of NAF-1 in cancer cells significantly enhanced cellular proliferation and tumor growth.. Thus it is determined that NAF-1 has a key role in cancer growth and prevention and its characteristics need to be explored for possible cancer cures.

Our Innovation

The technology to be developed is an innovative peptide drug  that will secure the reducing state of cells and organs to avoid damaging oxidative stress. It is based on a novel interaction of the recently characterized NEET protein, NAF‐1 with TXNIP, a Thioredoxin binding protein that inhibits the latter.

Advantages

  • Preferentially penetrates breast cancer cells & kills them
  • Optimized for the highest efficacy possible in-vivo in two distinct animal model systems of breast and prostate cancer

Technology

The anti-cancer peptide is derived from a new player in cancer, the NAF-1 protein, which plays a key role in TN breast cancer, prostate, ovary, pancreas gastric and other cancers. A fragment of NAF-1, 24-amino acids peptide, is the peptide-lead. This lead was partially optimized by preliminary Alanin scan and by substituting its L-amino acids (all or some) by D-amino acids. The studies to characterize its efficacy indicate that this peptide-lead does not penetrate and does not affect normal cell whereas it is highly efficient in killing malignant TN breast cancer cells in vitro and in preventing breast tumor progression in vivo in nude mice.

 

Figure 1 Overall structural organization of the homo-dimeric cytosol facing domains of the NEET proteins. A. A ribbon diagram of mitoNEET (red) and NAF‐1 (blue) proteins. The protomers of each protein, are packed in a parallel fashion with each protomer harboring a 2Fe‐2S cluster, depicted as yellow (sulfur) and red (iron) spheres. B. Superposition of the cluster binding regions of the two NEET proteins; the four amino acids coordinating the cluster are labele dwith their respective numbers in mNT and NAF‐1.

Opportunity

Initially, this peptide-based drug is anticipated to provide a cure for triple-negative breast cancer, which currently has no therapeutic solution. However, preliminary results indicate their efficacy in other cancer types as well, in addition to being a possible anti-microbial agent.

 

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608