Non-Toxic Motuporamine Analogues to Target Cancer Metastasis
Patent Number: US9266815
Executive Summary:
General Description:
Metastasis, the spreading of cancers to distant parts of the body, is one of the main causes of cancer-related deaths. However, most cancer drugs target cell proliferation and not metastasis. The disclosed motuporamine analogues have been shown to reduce the migration ability of metastatic human pancreatic cancer cells in vitro and reduce tumor growth and metastasis in a pancreatic cancer mouse model in vivo. Compared to the parent compound, the analogues exhibited increased anti-metastatic activity and reduced toxicity. Both of these properties have pharmacological benefits. In particular, increased potency of the compounds could lead to a lower required dosage regiment and reduced side effects.
Strengths:
Weaknesses:
Publications:
Muth A., Pandey V., Kaur N., Wason M., Baker C., Han X., Johnson T.R., Altomare D.A., Phanstiel O. 2014. Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives. J. Med. Chem. 57(10): 4023-4034. http://pubs.acs.org/doi/abs/10.1021/jm401906v
Patent Status:
Priority date: 03/28/2012
Filing date: 0 9/29/2014
Publication date: 02/26/2015
Grant date: 02/23/2016
Inventor Bio: Otto Phanstiel
https://med.ucf.edu/directory/otto-phanstiel-iv-ph-d-2/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Granted, Active
- Patent Link: https://patents.google.com/patent/US9266815/
- Research Institute: University of Central Florida
- Disease Focus: Metastatic cancers such as pancreatic cancers
- Basis of Invention: Novel motuporamine analogues with high anti-metastatic activity and low toxicity compared to the parent compounds
- How it works: Motuporamines are naturally occurring anti-cancer compounds isolated from the sea sponge Xestospongia exigua. The motuporamine scaffold consists of a macrocycle and an appended polyamine motif. By incrementally moving the polyamine chain away from the macrocycle structure, the anti-metastatic activity of the compound is increased and the toxicity is decreased
- Lead Challenge Inventor: Otto Phanstiel
- Inventors: Otto Phanstiel, Aaron Muth
- Development Stage: Pre-clinical (mouse model)
- Novelty: The motuporamine analogues innovatively extend the polyamine away from the macrocycle and use a carbocycle (all carbon-containing ring) over the nitrogen containing heterocycle of the parent compound. This structural modification improves the anti-metastatic activity of the compounds, while reducing their toxicity
- Clinical Applications: Treatment of metastatic cancers
General Description:
Metastasis, the spreading of cancers to distant parts of the body, is one of the main causes of cancer-related deaths. However, most cancer drugs target cell proliferation and not metastasis. The disclosed motuporamine analogues have been shown to reduce the migration ability of metastatic human pancreatic cancer cells in vitro and reduce tumor growth and metastasis in a pancreatic cancer mouse model in vivo. Compared to the parent compound, the analogues exhibited increased anti-metastatic activity and reduced toxicity. Both of these properties have pharmacological benefits. In particular, increased potency of the compounds could lead to a lower required dosage regiment and reduced side effects.
Strengths:
- Increased anti-metastatic activity
- Reduced toxicity
- Ease of synthesis via commercially available 15-membered ketones (eliminates the need for the lengthy synthesis of the motuporamine heterocycle)
Weaknesses:
- Preclinical stage (mouse model), additional animal studies required
Publications:
Muth A., Pandey V., Kaur N., Wason M., Baker C., Han X., Johnson T.R., Altomare D.A., Phanstiel O. 2014. Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives. J. Med. Chem. 57(10): 4023-4034. http://pubs.acs.org/doi/abs/10.1021/jm401906v
Patent Status:
Priority date: 03/28/2012
Filing date: 0 9/29/2014
Publication date: 02/26/2015
Grant date: 02/23/2016
Inventor Bio: Otto Phanstiel
https://med.ucf.edu/directory/otto-phanstiel-iv-ph-d-2/