A high-throughput screening campaign against PFKFB3 identified potential inhibitors with novel scaffolds

Li, Jie; Zhou, Yan; Eelen, Guy; Zhou, Qingtong; Feng, Wen-bo; Labroska, Viktorija; Ma, Fen-fen; Lu, Huiping; Dewerchin, Mieke; Carmeliet, Peter; Wang, Mingwei; Yang, Dehua

doi:10.1038/s41401-022-00989-1

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…PFKFB3 kinase inhibitory activity was measured using an ADP-Glo Kinase Assay kit (Promega) according to a published modified protocol [34]. Compound solution (1 µL, with a final concentration of 20 µM in 1% DMSO) and 2 µL enzyme solution were added to 384-well plates, followed by incubation at room temperature (RT) for 30 min.…”

Section: Pfkfb3 Kinase Inhibitory Activitymentioning

confidence: 99%

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040

Song,

She,

Chen

et al. 2023

Marine Drugs

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Five new fusarin derivatives, steckfusarins A–E (1–5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

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Section: Pfkfb3 Kinase Inhibitory Activitymentioning

confidence: 99%

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040

Song,

She,

Chen

et al. 2023

Marine Drugs

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Functions and novel regulatory mechanisms of key glycolytic enzymes in pulmonary arterial hypertension

Wang,

Liu,

Huang

et al. 2024

European Journal of Pharmacology

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High-throughput screen identifies non inflammatory small molecule inducers of trained immunity

Knight,

Ketter,

Ung

et al. 2024

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

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Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as β-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation—a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

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A high-throughput screening campaign against PFKFB3 identified potential inhibitors with novel scaffolds

Cited by 3 publications

References 47 publications

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040

New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040

Functions and novel regulatory mechanisms of key glycolytic enzymes in pulmonary arterial hypertension

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity

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