Cancer and Infectious Causes

Smith, Aaron; Oertle, John; Prato, Dino

doi:10.4236/ojmm.2014.43019

Cited by 2 publications

(1 citation statement)

References 162 publications

(140 reference statements)

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“…28 On the other hand, triclabendazole is a member of the benzimidazole family of anthelmintics which displays high efficacy against helminthiasis in both immature and adult live flukes especially related to hermaphroditic trematondes known as clonorchis sinensis . 29 Clonorchis sinensis can cause an inflammatory response that induces the likelihood of forming cholangiocarcinoma. 30 …”

Section: Resultsmentioning

confidence: 99%

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

et al. 2017

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Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that binds tumor necrosis factor or lymphotoxin-alpha and plays a critical role in regulating the inflammatory response. Upregulation of these ligands is associated with inflammatory and autoimmune diseases. Current treatments reduce symptoms by sequestering free ligands, but this can cause adverse side effects by unintentionally inhibiting ligand binding to off-target receptors. Hence, there is a need for new small molecules that specifically target the receptors, rather than the ligands. Here, we developed a TNFR1 FRET biosensor expressed in living cells to screen compounds from the NIH Clinical Collection. We used an innovative high-throughput fluorescence lifetime screening platform that has exquisite spatial and temporal resolution to identify two small-molecule compounds, zafirlukast and triclabendazole, that inhibit the TNFR1-induced IκBα degradation and NF-κB activation. Biochemical and computational docking methods were used to show that zafirlukast disrupts the interactions between TNFR1 pre-ligand assembly domain (PLAD), whereas triclabendazole acts allosterically. Importantly, neither compound inhibits ligand binding, proving for the first time that it is possible to inhibit receptor activation by targeting TNF receptor-receptor interactions. This strategy should be generally applicable to other members of the TNFR superfamily, as well as to oligomeric receptors in general.

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Section: Resultsmentioning

confidence: 99%

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

et al. 2017

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PathoDNA, an Advanced Diagnostic for Lyme Disease & Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity Than ELISA/Western Blot

Schettig¹,

Tan-Lim²,

Warren³

et al. 2021

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Cancer and Infectious Causes

Cited by 2 publications

References 162 publications

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

PathoDNA, an Advanced Diagnostic for Lyme Disease & Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity Than ELISA/Western Blot

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Cancer and Infectious Causes

Cited by 2 publications

References 162 publications

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors

PathoDNA, an Advanced Diagnostic for Lyme Disease &amp; Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity Than ELISA/Western Blot

Contact Info

Product

Resources

About

PathoDNA, an Advanced Diagnostic for Lyme Disease & Co-Infections Utilizing Next Generation DNA Sequencing with Greater Sensitivity and Selectivity Than ELISA/Western Blot