9,10-DIHYDRO-9,10[1',2']-BENZENOANTHRACENE-1,4-DIONE

Description

NFAT activation inhibitor III is a cell-permeant inhibitor of signaling through nuclear factor of activated T cells (NFAT). It binds the substrate recognition site of the phosphatase calcineurin (K_d = 0.8 μM), preventing it from binding and dephosphorylating NFAT. NFAT activation inhibitor III blocks the nuclear import of NFAT in T cells stimulated with ionomycin . It prevents the induced expression of cytokine mRNAs in T cells stimulated with phorbol ester and ionomycin.

Uses

INCA 6 inhibits nuclear factor of activated T cells (NFAT) dephosphorylation and nuclear import, which in turn, interferes with downstream targets of NFAT including induction of cytokine mRNAs.

Definition

ChEBI: LSM-2729 is an anthraquinone.

General Description

A cell-permeable, potent, and selective inhibitor of Calcineurin-NFAT (Nuclear Factor of Activated T cells) signaling. Binds to calcineurin with high affinity (K_d = 800 nM), disrupts its interaction with NFAT, and completely blocks calcineurin-dependent NFAT dephosphorylation, nuclear import (~40 μM in C1.7W2 T cells), and induction of NFAT-targeted cytokine mRNAs. Unlike CsA (Cat. No. 239835) and FK506, INCA-6 does not affect calcineurin activity or its downstream signaling.

Biological Activity

Inhibitor of interaction between calcineurin and its substrate nuclear factor of activated T cells (NFAT); blocks at the substrate recognition site but not at the catalytic site (K d = 0.8 mM). Inhibits NFAT dephosphorylation and nuclear import. Also prevents induction of cytokine mRNAs that are downstream targets of NFAT.

Biochem/physiol Actions

Cell permeable: yes

storage

Store at -20°C