ArticleFrontiers in pharmacology2022
Synthesis, Screening and Characterization of Novel Potent Arp2/3 Inhibitory Compounds Analogous to CK-666.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Conditional replacement of the mouse luteinizing hormone receptor with green fluorescent protein, enabling imaging of cell migration during ovulation.Endocrinology · 2026Article
- Conditional replacement of the mouse LH receptor with GFP, enabling imaging of cell migration during ovulation.bioRxiv : the preprint server for biology · 2026Article
- The Arp2/3 complex is required for in situ haptotactic response of microglia to iC3b.EMBO reports · 2026Article
- Migrastatics: an overview of the current scenario and future cancer treatments.Frontiers in oncology · 2026Review
- Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.Journal of molecular cell biology · 2024Article
- Tumor invasiveness is regulated by the concerted function of APC, formins, and Arp2/3 complex.iScience · 2024Article
- The Inhibition of Vessel Co-Option as an Emerging Strategy for Cancer Therapy.International journal of molecular sciences · 2024Review
- NHC-Ag(I) and NHC-Au(I) Complexes withACS medicinal chemistry letters · 2023Article
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9 authors.
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Abstract
Branched actin networks polymerized by the Actin-related protein 2 and 3 (Arp2/3) complex play key roles in force generation and membrane remodeling. These networks are particularly important for cell migration, where they drive membrane protrusions of lamellipodia. Several Arp2/3 inhibitory compounds have been identified. Among them, the most widely used is CK-666 (2-Fluoro-N-[2-(2-methyl-1H-indol-3-yl)ethyl]-benzamide), whose mode of action is to prevent Arp2/3 from reaching its active conformation. Here 74 compounds structurally related to CK-666 were screened using a variety of assays. The primary screen involved EdU (5-ethynyl-2'-deoxyuridine) incorporation in untransformed MCF10A cells. The resulting nine positive hits were all blocking lamellipodial protrusions and cell migration in B16-F1 melanoma cells in secondary screens, showing that cell cycle progression can be a useful read-out of Arp2/3 activity. Selected compounds were also characterized on sea urchin embryos, where Arp2/3 inhibition yields specific phenotypes such as the lack of triradiate spicules and inhibition of archenteron elongation. Several compounds were filtered out due to their toxicity in cell cultures or on sea urchin development. Two CK-666 analogs,
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