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New Inhibitors of Polo-like Kinase 1 (PLK1) as Anti-Cancer Agents

Description of Invention:
Tumor formation is the result of uncontrolled cellular growth and invasion. Polo-like kinase 1 (PLK1) is a regulator of cell growth whose overexpression has been associated with several types of cancer (e.g., breast cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma). It has been shown that inhibition of PLK1 causes cell death (apoptosis) in tumor cells but not normal cells. This suggested that inhibiting PLK1 could be an effective treatment for cancer patients without causing unwanted side-effects.

PLK1 contains a unique protein domain known as the polo box domain (PBD), which is essential for its function. One strategy for inhibiting PLK1 involves preventing the PBD domain from interacting with PLK1 substrates. A synthetic peptide with the ability to selectively bind to the PBD was recently identified. Using this peptide as a platform, NIH inventors have designed peptide mimetics that interact with the PBD with greater affinity than the wild-type peptide. By inhibiting PLK1 and selectively inducing apoptosis in cancer cells, these mimetics could serve as potential anti-cancer therapies.

  • New anti-cancer therapies that specifically target PLK1.
  • Platform for the development of further improved PLK1 inhibitors.

  • The peptide mimetics have an increased affinity for the polo box domain of PLK1 compared to the wild-type peptide, making them superior as inhibitors of PLK1.
  • The peptide mimetics provide greater metabolic stability and potential effectiveness over synthetic peptides prepared using coded amino acids.
  • Inhibiting PLK1 provides an opportunity for successful treatment of cancer with fewer side-effects because only tumor cells are killed.

Development Status:
Preclinical stage of development.

Terrence R Burke (NCI)
Fa Liu (NCI)
Kyung S Lee (NCI)
Jung-Eun Park (NCI)
Wen-Jian Qian (NCI)

Patent Status:
HHS, Reference No. E-181-2009/2
US, Application No. 13/320,726 filed 17 May 2010

Relevant Publication:
  1. F Liu et al. SAR by oxime-containing peptide libraries: application to Tsg101 ligand optimization. Chembiochem. 2008 Aug 11;9(12):2000-2004. [PMID: 18655064]
  2. F Liu et al. Protected aminooxyprolines for expedited library synthesis: Application to Tsg101-directed proline-oxime containing peptides. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1096-1101. [PMID: 18083557]
  3. PCT Application WO 2004/046317, "Crystal structure of human Polo-like kinase Plk1, Polo Box domain-binding phosphopeptide core sequences, and their therapeutic uses for cancer."

Licensing Status:
Available for licensing.

For Licensing Information Please Contact:
Patrick McCue Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: McCuepat@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220

Ref No: 1971

Updated: 06/2011


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