1-(3,6-Dibromo-9H-carbazol-9-yl)-3-(dimethylamino)propan-2-ol

Wiskostatin (253449-04-6) is a selective, reversible inhibitor of neural Wiskott-Aldrich syndrome protein (N-WASP) activity1. Binds to the regulatory domain of N-WASP and inhibits activation of Arp2/3 complex by forcing N-WASP into an inactive conformation2. Inhibits PIP2-induced actin polymerization (EC50=4 μM). Wiskostatin perturbs agrin-elicited acetylcholine receptor clustering3. Inhibits the formation of dendritic spines and synapses in hippocampal neurons.

Wiskostatin has been used:

• as a small-molecule inhibitor of Wiskott-Aldrich syndrome protein (WASP) in human osteosarcoma U2OS cells and mouse-tail fibroblast cell lines
• as a neural (N)-WASP inhibitor in cultured neurons and in the human embryonic kidney (HEK293) cells expressing HA-Parkin
• as a neural (N)-WASP inhibitor in dorsal root ganglion (DRG) cells to investigate vascular endothelial growth factor (VEGF) effect on the actin related protein 2/3 complex (Arp 2/3)

ChEBI: 1-(3,6-dibromocarbazol-9-yl)-3-(dimethylamino)propan-2-ol is a member of the class of carbazoles that is 1-(carbazol-9-yl)-3-(dimethylamino)propan-2-ol bearing two additional bromo substituents at positions 3 and 6 on the carbazole ring system. It is a member of carbazoles, an organobromine compound, a secondary alcohol and a tertiary amino compound.

Wiskostatin is a dibrominated carbazole. The N-alkylated side chain has a chiral hydroxyl group and a terminal tertiary amine.

Wiskostatin is a selective inhibitor of N-WASP, a ubiquitously expressed member of the Wiskott-Aldrich Syndrome protein (WASp) family that regulates actin polymerization. Wiskostatin inhibits actin-dependent cellular functions, including migration, transmembrane transport and phagocytosis.

+4°C

[1] JEFFREY R PETERSON  Timothy J M. Small molecules, big impact: a history of chemical inhibitors and the cytoskeleton.[J]. Chemistry & biology, 2002, 9 12: 1275-1285. DOI:10.1016/s1074-5521(02)00284-3
[2] JEFFREY R PETERSON. Chemical inhibition of N-WASP by stabilization of a native autoinhibited conformation[J]. Nature Structural & Molecular Biology, 2004, 11 8: 747-755. DOI:10.1038/nsmb796
[3] ANNIE CARTAUD. Agrin triggers the clustering of raft-associated acetylcholine receptors through actin cytoskeleton reorganization.[J]. Biology of the Cell, 2011, 103 6: 287-301. DOI:10.1042/bc20110018
[4] ADAM M WEGNER. N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses.[J]. The Journal of Biological Chemistry, 2008: 15912-15920. DOI:10.1074/jbc.m801555200