Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide
Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10054 |
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| author | Michael P. Dempsey Katelyn E. Andersen Brittney M. Wells Mitchell A. Taylor Clay L. Cashman Lesley B. Conrad Claire A. Kearney Mary B. Conklin Emily R. Via Emily M. Doe Ravikiran Komirisetty Susan Dearborn Srinivasa T. Reddy Robin Farias-Eisner |
| author_facet | Michael P. Dempsey Katelyn E. Andersen Brittney M. Wells Mitchell A. Taylor Clay L. Cashman Lesley B. Conrad Claire A. Kearney Mary B. Conklin Emily R. Via Emily M. Doe Ravikiran Komirisetty Susan Dearborn Srinivasa T. Reddy Robin Farias-Eisner |
| author_sort | Michael P. Dempsey |
| collection | DOAJ |
| description | Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug–drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women’s health crisis of epithelial carcinomas of the ovary and colon. |
| first_indexed | 2024-03-11T02:21:43Z |
| format | Article |
| id | doaj.art-a9fea4954a5c485995cfa2ee4815e9f5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:21:43Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a9fea4954a5c485995cfa2ee4815e9f52023-11-18T10:47:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121005410.3390/ijms241210054Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic PeptideMichael P. Dempsey0Katelyn E. Andersen1Brittney M. Wells2Mitchell A. Taylor3Clay L. Cashman4Lesley B. Conrad5Claire A. Kearney6Mary B. Conklin7Emily R. Via8Emily M. Doe9Ravikiran Komirisetty10Susan Dearborn11Srinivasa T. Reddy12Robin Farias-Eisner13School of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USASchool of Medicine, Creighton University, Omaha, NE 68178, USADepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, The University of California at Los Angeles, Los Angeles, CA 90095, USACharles River Laboratories International, Stone Ridge, NY 12484, USADepartment of Medicine, Division of Cardiology, David Geffen School of Medicine, The University of California at Los Angeles, Los Angeles, CA 90095, USASchool of Medicine, Creighton University, Omaha, NE 68178, USAEpithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug–drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women’s health crisis of epithelial carcinomas of the ovary and colon.https://www.mdpi.com/1422-0067/24/12/10054ovarian epithelial adenocarcinomacolonic epithelial adenocarcinomanovel cancer treatmentdrug innovationstability |
| spellingShingle | Michael P. Dempsey Katelyn E. Andersen Brittney M. Wells Mitchell A. Taylor Clay L. Cashman Lesley B. Conrad Claire A. Kearney Mary B. Conklin Emily R. Via Emily M. Doe Ravikiran Komirisetty Susan Dearborn Srinivasa T. Reddy Robin Farias-Eisner Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide International Journal of Molecular Sciences ovarian epithelial adenocarcinoma colonic epithelial adenocarcinoma novel cancer treatment drug innovation stability |
| title | Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide |
| title_full | Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide |
| title_fullStr | Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide |
| title_full_unstemmed | Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide |
| title_short | Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide |
| title_sort | stability characterization of the novel anti cancer hm 10 10 hdl mimetic peptide |
| topic | ovarian epithelial adenocarcinoma colonic epithelial adenocarcinoma novel cancer treatment drug innovation stability |
| url | https://www.mdpi.com/1422-0067/24/12/10054 |
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