Description
Cytochrome
c, which leaks from the mitochondrial intermembrane space into the cytosol, causes oligomerization of apoptotic protease-activating factor 1 (Apaf-1), forming a caspase activation complex known as the apoptosome. NS3694 is a cell-permeable diarylurea compound that inhibits apoptosome formation and caspase activation. It blocks cytochrome
c-induced caspase activation in HeLa cell cytosolic extracts with an IC
50 value of approximately 50 μM. NS3694 prevents the formation of apoptosomes, which prevents the association of procaspases with Apaf-1. It suppresses caspase activation and apoptosis in cells treated with either TNF-α or staurosporine . NS3694 is used to examine the role of apoptosome-mediated caspase activation in cell death.
Uses
NS3694 is a suppressor of the formation of apoptosome Apaf-1.
Definition
ChEBI: 4-chloro-2-[[oxo-[3-(trifluoromethyl)anilino]methyl]amino]benzoic acid is a member of ureas.
in vitro
previous study found that ns3694, and its two analogs (ns1764 and ns1784) were well-tolerated by mcf-7s1 breast cancer cells at concentrations up to 100, 50, and 25 μm, respectively. moreove, all three compounds could not inhibit recombinant caspase 9 and caspase 3 at concentrations ranging from 25 to 100 μm. in addition, ns3694 was able to inhibit the co-immunoprecipitation of caspase 9 and apaf-1 from hela cell cytosol stimulated by cytochrome c and datp. ns3694 could also inhibit the formation of the active 700-kda apoptosome complex, but had no effect on tnf-induced caspase-independent death of wehi-s cells. ns3694 did not inhibit fasl-induced caspase activation or death in type i cells neither [1].
IC 50
approximately 50 μm for cytochrome c-induced caspase activation in hela cell cytosolic extracts
References
[1] lademann, u. ,cain, k.,gyrd-hansen, m., et al. diarylurea compounds inhibit caspase activation by preventing the formation of the active 700-kilodalton apoptosome complex. mol.cell biol. 23(21), 7829-7837 (2003).
