Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation

The discoidin domain receptor tyrosine kinases DDR1 and DDR2 are distinguished from other kinase enzymes by their extracellular domains, which interact with collagen rather than with peptidic growth factors, before initiating signaling via tyrosine phosphorylation. They share significant sequence an...

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Autores principales:	William A. Denny, Jack U. Flanagan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	small molecules selectivity DDR kinase inhibitors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3d373c76557544568673f60d030c67a7
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spelling	oai:doaj.org-article:3d373c76557544568673f60d030c67a72021-11-25T16:53:38ZInhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation10.3390/biom111116712218-273Xhttps://doaj.org/article/3d373c76557544568673f60d030c67a72021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1671https://doaj.org/toc/2218-273XThe discoidin domain receptor tyrosine kinases DDR1 and DDR2 are distinguished from other kinase enzymes by their extracellular domains, which interact with collagen rather than with peptidic growth factors, before initiating signaling via tyrosine phosphorylation. They share significant sequence and structural homology with both the c-Kit and Bcr-Abl kinases, and so many inhibitors of those kinases are also effective. Nevertheless, there has been an extensive research effort to develop potent and specific DDR inhibitors. A key interaction for many of these compounds is H-bonding to Met-704 in a hydrophobic pocket of the DDR enzyme. The most widespread use of DDR inhibitors has been for cancer therapy, but they have also shown effectiveness in animal models of inflammatory conditions such as Alzheimer’s and Parkinson’s diseases, and in chronic renal failure and glomerulonephritis.William A. DennyJack U. FlanaganMDPI AGarticlesmall moleculesselectivityDDR kinase inhibitorsMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1671, p 1671 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	small molecules selectivity DDR kinase inhibitors Microbiology QR1-502
spellingShingle	small molecules selectivity DDR kinase inhibitors Microbiology QR1-502 William A. Denny Jack U. Flanagan Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
description	The discoidin domain receptor tyrosine kinases DDR1 and DDR2 are distinguished from other kinase enzymes by their extracellular domains, which interact with collagen rather than with peptidic growth factors, before initiating signaling via tyrosine phosphorylation. They share significant sequence and structural homology with both the c-Kit and Bcr-Abl kinases, and so many inhibitors of those kinases are also effective. Nevertheless, there has been an extensive research effort to develop potent and specific DDR inhibitors. A key interaction for many of these compounds is H-bonding to Met-704 in a hydrophobic pocket of the DDR enzyme. The most widespread use of DDR inhibitors has been for cancer therapy, but they have also shown effectiveness in animal models of inflammatory conditions such as Alzheimer’s and Parkinson’s diseases, and in chronic renal failure and glomerulonephritis.
format	article
author	William A. Denny Jack U. Flanagan
author_facet	William A. Denny Jack U. Flanagan
author_sort	William A. Denny
title	Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
title_short	Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
title_full	Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
title_fullStr	Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
title_full_unstemmed	Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
title_sort	inhibitors of discoidin domain receptor (ddr) kinases for cancer and inflammation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3d373c76557544568673f60d030c67a7
work_keys_str_mv	AT williamadenny inhibitorsofdiscoidindomainreceptorddrkinasesforcancerandinflammation AT jackuflanagan inhibitorsofdiscoidindomainreceptorddrkinasesforcancerandinflammation
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Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation

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