The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Selective inhibition of prolyl 4-hydroxylases by bipyridinedicarboxylates
Abstract
Collagen is the most abundant protein in animals. A variety of indications are associated with the overproduction of collagen, including fibrotic diseases and cancer metastasis. The stability of collagen relies on the posttranslational modification of proline residues to form (2S,4R)-4-hydroxyproline. This modification is catalyzed by collagen prolyl 4-hydroxylases (CP4Hs), which are Fe(II)- and α-ketoglutarate (AKG)-dependent dioxygenases located in the lumen of the endoplasmic reticulum. Human CP4Hs are validated targets for treatment of both fibrotic diseases and metastatic breast cancer. Herein, we report on 2,2′-bipyridinedicarboxylates as inhibitors of a human CP4H. Although most 2,2′-bipyridinedicarboxylates are capable of inhibition via iron sequestration, the 4,5′- and 5,5′-dicarboxylates were found to be potent competitive inhibitors of CP4H, and the 5,5′-dicarboxylate was selective in its inhibitory activity. Our findings clarify a strategy for developing CP4H inhibitors of clinical utility.
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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 [20]
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“Whereas bipy itself does not serve as an activator of CP4H,20,22”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [20]
In the citing paper
“Bipy-4,5′-dicarboxylate (bipy45′DC) and bipy-5,5′-dicarboxylate (bipy55′DC) are potent inhibitors of human CP4H1 and thought to inhibit the enzyme by competing with α-ketoglutarate.20”
From Human Collagen Prolyl 4-Hydroxylase Is Activated by Ligands for Its Iron Center (2016) · cites this paper as [20]
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“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 [20]
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Self-citation
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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-citationSelective Inhibition of Collagen Prolyl 4-Hydroxylase in Human Cells
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Self-citationHuman 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., & Raines, R. T.
- Venue
- Bioorganic & Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 23
- Issue
- 13
- Pages
- 3081-3090
- ISSN
- 0968-0896
- PMC
- PMC4552733
- Cited by
- 16
- References
- 36
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 339 d)
- Funders
- NIH (R01 AR044276, T32 GM007215, P41 GM103399)
- NSF (CHE-9974839)
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