Uses
Windorphen is a selective inhibitor of p300 histone acetyltransferase, a coactivator that associates withβ-catenin,blocking the Wnt signal required for ventral development.
Biological Activity
windorphen is a wnt inhibitor that selectively abrogates the wnt signaling for ventral development.wnt protein is a family of signaling proteins that interacts on the wnt/β-catenin pathways during embryotic development, cell proliferation, migration and adult tissue homeostasis.in canonical wnt/β-catenin reporter cell line stf293, windorphen dose-dependently inhibits wnt3a-inducible topflash-luciferase activity (ic50 of 1.5 mm). in human colon adenocarcinomasw480 cells with defective apc gene that constitutively activates wnt signaling, 72 h treatment of windorphen causes a wide spread apoptosis. [1]in zebrafish embryos, windorphen leads to apparent expansion of the dorsal markers (pax2.1) and marker of rhombomeres 3 and 5 at the six-somite stage (krox0). windorphen selectively inhibits wnt signaling in ventral and lateral regions of the 50% epiboly stage embryo (5.3 hpf). in addition, windoprhen treatment rescues the telencephalon/eye phenotype in the mbl mutant zebrafish (i.e. a defective axin1/β-catenin destruction complex causes abnormal activation of wnt signaling and the loss of telencephalon and eyes.) [1]
References
1. hao j, ao a, zhou l et al. selective small molecule targeting β-catenin function discovered by invivo chemical genetic screen. cell rep. 2013 sep 12;4(5):898-904.
