NS 3694

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 IC₅₀ 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).