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Advances in the discovery of cathepsin K inhibitors on bone resorption

Cathepsin K (Cat K), highly expressed in osteoclasts, is a cysteine protease member of the cathepsin lysosomal protease family and has been of increasing interest as a target of medicinal chemistry efforts for its role in bone matrix degradation. Inhibition of the Cat K enzyme reduces bone resorptio...

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Autores principales: Lu, Jun, Wang, Maolin, Wang, Ziyue, Fu, Zhongqi, Lu, Aiping, Zhang, Ge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010086/
https://www.ncbi.nlm.nih.gov/pubmed/29723068
http://dx.doi.org/10.1080/14756366.2018.1465417
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author Lu, Jun
Wang, Maolin
Wang, Ziyue
Fu, Zhongqi
Lu, Aiping
Zhang, Ge
author_facet Lu, Jun
Wang, Maolin
Wang, Ziyue
Fu, Zhongqi
Lu, Aiping
Zhang, Ge
author_sort Lu, Jun
collection PubMed
description Cathepsin K (Cat K), highly expressed in osteoclasts, is a cysteine protease member of the cathepsin lysosomal protease family and has been of increasing interest as a target of medicinal chemistry efforts for its role in bone matrix degradation. Inhibition of the Cat K enzyme reduces bone resorption and thus, has rendered the enzyme as an attractive target for anti-resorptive osteoporosis therapy. Over the past decades, considerable efforts have been made to design and develop highly potent, excellently selective and orally applicable Cat K inhibitors. These inhibitors are derived from synthetic compounds or natural products, some of which have passed preclinical studies and are presently in clinical trials at different stages of advancement. In this review, we briefly summarised the historic development of Cat K inhibitors and discussed the relationship between structures of inhibitors and active sites in Cat K for the purpose of guiding future development of inhibitors.
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spelling pubmed-60100862018-07-11 Advances in the discovery of cathepsin K inhibitors on bone resorption Lu, Jun Wang, Maolin Wang, Ziyue Fu, Zhongqi Lu, Aiping Zhang, Ge J Enzyme Inhib Med Chem Research Paper Cathepsin K (Cat K), highly expressed in osteoclasts, is a cysteine protease member of the cathepsin lysosomal protease family and has been of increasing interest as a target of medicinal chemistry efforts for its role in bone matrix degradation. Inhibition of the Cat K enzyme reduces bone resorption and thus, has rendered the enzyme as an attractive target for anti-resorptive osteoporosis therapy. Over the past decades, considerable efforts have been made to design and develop highly potent, excellently selective and orally applicable Cat K inhibitors. These inhibitors are derived from synthetic compounds or natural products, some of which have passed preclinical studies and are presently in clinical trials at different stages of advancement. In this review, we briefly summarised the historic development of Cat K inhibitors and discussed the relationship between structures of inhibitors and active sites in Cat K for the purpose of guiding future development of inhibitors. Taylor & Francis 2018-05-03 /pmc/articles/PMC6010086/ /pubmed/29723068 http://dx.doi.org/10.1080/14756366.2018.1465417 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Lu, Jun
Wang, Maolin
Wang, Ziyue
Fu, Zhongqi
Lu, Aiping
Zhang, Ge
Advances in the discovery of cathepsin K inhibitors on bone resorption
title Advances in the discovery of cathepsin K inhibitors on bone resorption
title_full Advances in the discovery of cathepsin K inhibitors on bone resorption
title_fullStr Advances in the discovery of cathepsin K inhibitors on bone resorption
title_full_unstemmed Advances in the discovery of cathepsin K inhibitors on bone resorption
title_short Advances in the discovery of cathepsin K inhibitors on bone resorption
title_sort advances in the discovery of cathepsin k inhibitors on bone resorption
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010086/
https://www.ncbi.nlm.nih.gov/pubmed/29723068
http://dx.doi.org/10.1080/14756366.2018.1465417
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