The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Selective Inhibition of Collagen Prolyl 4-Hydroxylase in Human Cells
Abstract
Collagen is the most abundant protein in animals. Its overproduction is associated with fibrosis and cancer metastasis. The stability of collagen relies on post-translational modifications, the most prevalent being the hydroxylation of collagen strands by collagen prolyl 4-hydroxylases (CP4Hs). Catalysis by CP4Hs enlists an iron cofactor to convert proline residues to 4-hydroxyproline residues, which are essential for the conformational stability of mature collagen. Ethyl 3,4-dihydroxybenzoate (EDHB) is commonly used as a "P4H" inhibitor in cells, but suffers from low potency, poor selectivity, and off-target effects that cause iron deficiency. Dicarboxylates of 2,2'-bipyridine are among the most potent known CP4H inhibitors but suffer from a high affinity for free iron. A screen of biheteroaryl compounds revealed that replacing one pyridyl group with a thiazole moiety retains potency and enhances selectivity. A diester of 2-(5-carboxythiazol-2-yl)pyridine-5-carboxylic acid is bioavailable to human cells and inhibits collagen biosynthesis at concentrations that neither cause general toxicity nor disrupt iron homeostasis. These data anoint a potent and selective probe for CP4H and a potential lead for the development of a new class of antifibrotic and antimetastatic agents.
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“Recently, we reported that certain dicarboxylate derivatives of 2,2′-bipyridine (bipy) and other biheteroaryl compounds are specific inhibitors of human CP4H.20,21”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [21]
In the citing paper
“These biheteroaryl dicarboxylates compete with α-ketoglutarate for binding to the active-site iron.”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [21]
In the citing paper
“For example, a thiazole analog (pythi) is a potent competitive inhibitor of CP4H1, whereas a pyrazole analog (pypyr) is not.”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [21]
In the citing paper
“Moreover, the bipy core in these molecules can be replaced with chelating biheteroaryls.21”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [21]
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Cites
1 retracted
RETRACTED: Collagen Prolyl Hydroxylases Are Essential for Breast Cancer Metastasis
Gilkes, D. M., Chaturvedi, P., Bajpai, S., Wong, C. C., Wei, H., Pitcairn, S., Hubbi, M. E., Wirtz, D., & Semenza, G. L. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3963 · Cited by 296
RetractedMolecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin
Aziz, J., Shezali, H., Radzi, Z., Yahya, N. A., Abu Kassim, N. H., Czernuszka, J., & Rahman, M. T. (2016) · Skin Pharmacology and Physiology · doi:10.1159/000447017 · Cited by 7,323
Collagen Structure and Stability
Shoulders, M. D., & Raines, R. T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.032207.120833 · Cited by 3,923
Self-citationDioxygen Activation at Mononuclear Nonheme Iron Active Sites: Enzymes, Models, and Intermediates
Costas, M., Mehn, M. P., Jensen, M. P., & QUE, L. J. (2004) · Chemical Reviews · doi:10.1021/cr020628n · Cited by 2,511
Collagen density promotes mammary tumor initiation and progression
Provenzano, P. P., Inman, D. R., Eliceiri, K. W., Knittel, J. G., Yan, L., Rueden, C. T., White, J. G., & Keely, P. J. (2008) · BMC Medicine · doi:10.1186/1741-7015-6-11 · Cited by 1,361
Aligned Collagen Is a Prognostic Signature for Survival in Human Breast Carcinoma
Conklin, M. W., Eickhoff, J. C., Riching, K. M., Pehlke, C. A., Eliceiri, K. W., Provenzano, P. P., Friedl, A., & Keely, P. J. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2010.11.076 · Cited by 1,321
Collagens, modifying enzymes and their mutations in humans, flies and worms
Myllyharju, J., & Kivirikko, K. I. (2003) · Trends in Genetics · doi:10.1016/j.tig.2003.11.004 · Cited by 1,235
Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related Enzymes
Hausinger, R. P. (2004) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230490440541 · Cited by 937
FORMATION AND STABILITY OF INORGANIC COMPLEXES IN SOLUTION
Job, P. (1928) · Cited by 742
Muckenthaler, M. U., Galy, B., & Hentze, M. W. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155521 · Cited by 701
Research works printed but not linked: 3
- 10.1042/bj3530333 · DOI
- Sasaki T., 1987, J. Invest. Dermatol., 262, 9397
- Job P., 1928, Annali di Chimica Applicata, 9, 113
Cited by
Collagen Prolyl 4-Hydroxylase as a Therapeutic Target: Miniperspective
Vasta, J. D., & Raines, R. T. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00822 · Cited by 82
Self-citationImpact of Reactive Species on Amino Acids—Biological Relevance in Proteins and Induced Pathologies
Andrés, C. M. C., Pérez de la Lastra, J. M., Andrés Juan, C., Plou, F. J., & Pérez-Lebeña, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214049 · Cited by 71
Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center
Vasta, J. D., & Raines, R. T. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00251 · Cited by 36
Self-citation
Metadata
- Authors
- Vasta, J. D., Andersen, K. A., Deck, K. M., Nizzi, C. P., Eisenstein, R. S., & Raines, R. T.
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-11-19
- Volume
- 11
- Issue
- 1
- Pages
- 193-199
- ISSN
- 1554-8929
- 1554-8937
- PMC
- PMC4798942
- Cited by
- 41
- References
- 53
- Language
- en
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK066600)
- Pharmaceutical Research and Manufacturers of America Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR044276)
- National Institute of General Medical Sciences (P41 GM103399, T32 GM007215, T32 GM008688)
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
