Fascin Inhibitors

Fascin is the actin-bundling protein. It influences tumor invasion and metastasis, filopodia formation, cell-shape changes and cell migration. Small molecules, fascin-pathway modulators (blockers and enhancers) are identified in a cell-based assay.

Download the list of available compounds active in the fascin bioassay.

Fragmental and structure similarity searchers are available based on all or selected active compounds. Please inquire customized subsets.

The list of names:

Acetylcysteine
Acetyltryptophan
Adiphenine
Amantadine
Aminolevulinic Acid
Anisindione
Apigenin
Azadirachtin
Baclofen
Benzyl Isothiocyanate
Bithionol
Broxyquinoline
Caffeine
Citrinin
Cloxyquin
Colchiceine
Colchicine
Cyclocreatine
Diflunisal
Droperidol
Dyclonine
Dyphylline
Emetine
Estradiol
Geneticin
Griseofulvin
Hydroxytacrine Maleate
Juglone
Mephenesin
Naproxen
Nateglinide
Nifedipine
Oxaprozin
Oxcarbazepine
Oxybenzone
Paclitaxel
Palmatine
Picropodophyllotoxin
Prednisolone
Propylthiouracil
Salicin
Sarafloxacin
S-Nitroso-N-Acetylpenicillamine
Spaglumic Acid
Spiperone
Sulfamethazine
Sulfamethoxazole
Sulfasalazine
Tannic Acid
Telenzepine
Thiothixene
Tolbutamide
Tranilast
Triadimefon
Vinburnine

Reference

Kraft R., Kahn A., et. al. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions. Disease Models & Mechanisms 6, 217-235 (2013) doi:10.1242/dmm.008243

Summary

The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the ‘filagree’ phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for

filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascinpathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the ‘beads-on-a-string’ defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function,

bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery.