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Mar. Drugs 2017, 15(9), 290; doi:10.3390/md15090290

Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, FL 32610, USA
Marine Science Institute, College of Science, University of the Philippines, Diliman, Quezon City 1100, Philippines
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA
Smithsonian Marine Station, 701 Seaway Drive, Fort Pierce, FL 34949, USA
Author to whom correspondence should be addressed.
Received: 1 April 2017 / Revised: 24 August 2017 / Accepted: 11 September 2017 / Published: 16 September 2017
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)
View Full-Text   |   Download PDF [2413 KB, uploaded 16 September 2017]   |  


Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0.19, 0.36 and 0.28 μM, respectively. Due to the significance of these proteases in cancer progression and metastasis, as well as their functional redundancy with respect to targeting overlapping substrates, we examined the effect of kempopeptin C on the downstream cellular substrates of matriptase: CDCP1 and desmoglein-2 (Dsg-2). Kempopeptin C was shown to inhibit the cleavage of both substrates in vitro. Additionally, kempopeptin C reduced the cleavage of CDCP1 in MDA-MB-231 cells up to 10 µM. The functional relevance of targeting matriptase and related proteases was investigated by assessing the effect of kempopeptin C on the migration of breast cancer cells. Kempopeptin C inhibited the migration of the invasive MDA-MB-231 cells by 37 and 60% at 10 and 20 µM, respectively. View Full-Text
Keywords: marine cyanobacteria; serine proteases; migration; breast cancer marine cyanobacteria; serine proteases; migration; breast cancer

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Al-Awadhi, F.H.; Salvador, L.A.; Law, B.K.; Paul, V.J.; Luesch, H. Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer. Mar. Drugs 2017, 15, 290.

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