Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer
© 2016 Japan Society for Bioscience, Biotechnology, and Agrochemistry.Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13....
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Published: |
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/58851 |
| _version_ | 1848760358115737600 |
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| author | Kothapalli, R. Siveen, K. Tan, T. Thiery, J. Kumar, A. Sethi, Gautam Swaminathan, K. |
| author_facet | Kothapalli, R. Siveen, K. Tan, T. Thiery, J. Kumar, A. Sethi, Gautam Swaminathan, K. |
| author_sort | Kothapalli, R. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2016 Japan Society for Bioscience, Biotechnology, and Agrochemistry.Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13. Two of six lead compounds, compound 5 (2,3-dihydro-1,4-benzodioxine- 5-carboxylic acid) and compound 6 (1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid) exhibited considerable inhibitory activity against MMP-13. Complementing to this study, we have also shown the gene expression levels of MMP-13 within the subtypes of colon and breast cancers classified from patients' tissue samples to provide a better understanding on which subtype of breast cancer patients would get benefited by MMP-13 inhibitors. Our current results show that compounds 5 and 6 could effectively inhibit MMP-13 and provide specific therapeutic possibilities in the treatment of inflammatory disorders and cancers. The characterization of these lead compounds would provide a better mechanistic understanding of exosite-based inhibition of MMP-13, which could overcome the challenges in the identification of other MMP catalytic domain-specific inhibitors. |
| first_indexed | 2025-11-14T10:14:30Z |
| format | Journal Article |
| id | curtin-20.500.11937-58851 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:14:30Z |
| publishDate | 2016 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-588512017-11-28T06:37:22Z Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer Kothapalli, R. Siveen, K. Tan, T. Thiery, J. Kumar, A. Sethi, Gautam Swaminathan, K. © 2016 Japan Society for Bioscience, Biotechnology, and Agrochemistry.Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13. Two of six lead compounds, compound 5 (2,3-dihydro-1,4-benzodioxine- 5-carboxylic acid) and compound 6 (1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid) exhibited considerable inhibitory activity against MMP-13. Complementing to this study, we have also shown the gene expression levels of MMP-13 within the subtypes of colon and breast cancers classified from patients' tissue samples to provide a better understanding on which subtype of breast cancer patients would get benefited by MMP-13 inhibitors. Our current results show that compounds 5 and 6 could effectively inhibit MMP-13 and provide specific therapeutic possibilities in the treatment of inflammatory disorders and cancers. The characterization of these lead compounds would provide a better mechanistic understanding of exosite-based inhibition of MMP-13, which could overcome the challenges in the identification of other MMP catalytic domain-specific inhibitors. 2016 Journal Article http://hdl.handle.net/20.500.11937/58851 10.1080/09168451.2016.1200456 restricted |
| spellingShingle | Kothapalli, R. Siveen, K. Tan, T. Thiery, J. Kumar, A. Sethi, Gautam Swaminathan, K. Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title | Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title_full | Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title_fullStr | Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title_full_unstemmed | Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title_short | Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - Experimental validation in human breast and colon cancer |
| title_sort | functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (mmp-13) - experimental validation in human breast and colon cancer |
| url | http://hdl.handle.net/20.500.11937/58851 |