Suramin: Clinical Uses and Structure-Activity Relationships

McGeary, Ross P.; Bennett, Andrew J.; Tran, Quoc Ba; Cosgrove, Kelly L.; Ross, Benjamin P.

doi:10.2174/138955708786369573

Cited by 110 publications

(101 citation statements)

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“…One caveat is that suramin has many cellular targets (12), presumably because of its ability to bind highly positively charged regions that are analogous to the cullin conserved basic canyon. However, analyses of suramin analogs (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Suramin has been used as the drug of choice for the treatment of African trypanosomiasis since 1924. It possesses antitumor activity (12) and also has been observed to reverse autism-like behaviors in mice (42). The mechanism of suramin in the treatment of trypanosomiasis is presently unknown.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of this assay format, a high-throughput screen (HTS) was performed, resulting in the identification of a potent inhibitor of CRL activity, suramin. Interestingly, suramin is a century-old antitrypansomal drug that also possesses antitumor activity (12).…”

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confidence: 99%

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Suramin inhibits cullin-RING E3 ubiquitin ligases

Chong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cullin-RING E3 ubiquitin ligases (CRL) control a myriad of biological processes by directing numerous protein substrates for proteasomal degradation. Key to CRL activity is the recruitment of the E2 ubiquitin-conjugating enzyme Cdc34 through electrostatic interactions between E3′s cullin conserved basic canyon and the acidic C terminus of the E2 enzyme. This report demonstrates that a smallmolecule compound, suramin, can inhibit CRL activity by disrupting its ability to recruit Cdc34. Suramin, an antitrypansomal drug that also possesses antitumor activity, was identified here through a fluorescence-based high-throughput screen as an inhibitor of ubiquitination. Suramin was shown to target cullin 1's conserved basic canyon and to block its binding to Cdc34. Suramin inhibits the activity of a variety of CRL complexes containing cullin 2, 3, and 4A. When introduced into cells, suramin induced accumulation of CRL substrates. These observations help develop a strategy of regulating ubiquitination by targeting an E2-E3 interface through small-molecule modulators.protein degradation | K48-polyubiquitination | E3 ligase | E2 enzyme | suramin

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Suramin inhibits cullin-RING E3 ubiquitin ligases

Chong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, successful drugs may require a degree of polypharmacology to have a therapeutic effect, whilst chemical probes require a degree of selectivity for meaningful interpretation of the experimental data (e.g. suramin versus the NF compounds mentioned previously) [40]. However, medicinal chemistry programmes do provide many of the compounds for research from both high-throughput campaigns and by optimising and then abandoning chemical series.…”

Section: Drug Discovery Programme Compoundsmentioning

confidence: 99%

Development of a comprehensive set of P2 receptor pharmacological research compounds

Felix¹,

Martin²,

Pinion³

et al. 2011

Purinergic Signalling

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Pharmacological manipulation of P2X and P2Y receptors has been critical to the elucidation of the biological roles of these receptors within a multitude of physiological and pathological processes. Initial purinergic signalling research made use of compounds based on pyridoxal phosphate, suramin and nucleotide analogues; recently developed compounds are often derivatives of these early tools. Tocris Bioscience first entered the field of purinergic signalling reagents with the commercial release of the pyridoxal phosphate derivative, iso-PPADS. During the past two decades, Tocris has assembled a collection of over 50 compounds for P2 receptor modulation, including research tools commercialised from both academic and industrial laboratories. Recently, a number of P2X subtypeselective compounds have been generated by pharmaceutical company medicinal chemistry programmes, supplementing our range of P2Y-selective compounds. Here, we detail the current, commercially available agonists and antagonists of P2X 1,2/3,3,4,7 and P2Y 1,6,11,12 receptors; considered together, they form the foundations of a comprehensive P2 receptor pharmacological 'toolkit'.

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“…To inhibit fibrosis formation following severe injury, attributed in large part to the secretion of transforming growth factor (TGF)-1 [10], researchers have investigated the administration of TGF-1 specific inhibitors, such as relaxin [11], decorin [12], and suramin [13][14][15]. In animal models, the presence of TGF-1 antagonists has significantly decreased fibrosis while concomitantly improving myofiber regeneration [11,16]. Ultrastructural changes were further associated with an increased force-producing capacity of the injured muscle [13].…”

Section: Regenerative Medicine Approachmentioning

confidence: 99%