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Table 1 Low molecular weight inhibitors of calcineurin-NFATc signalling

From: Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

Inhibitor Mode of action IC50/Kd*/Ki** References
General protein phosphatase inhibitors inhibiting also calcineurin (CaN)
Endothall binds to the active centre of PP1, PP2A, CaN 11,5 μM** a Tatlock JH 1997 [195]
FMPP binds covalently to the active centre of PP1, PP2A, CaN 44 mMb Born TL 1995 [88]
Norcantharidin binds to the active centre of PP1, PP2A, CaN 31 μMb Steward SG 2007 [90]
Okadaic acid binds to the active centre of PP1, PP2A, CaN 4.6 μMb Bialojan C 1988 [196]
Tyrphostins bind possibly to the active centre of PP1, PP2A, CaN 21 - 62 μMb Martin BL 1998 [89]
Inhibitors of calcineurin-dependent signalling - CsA, FK506 and derivatives
CsA/CypA complex blocks substrate access to the active centre of CaN 7 nMa Fruman DA 1992 [197]
ISA247/CypA complex blocks substrate access to the active centre of CaN ~100 nMa Aspeslet L 2001 [75]
[Dat-Sar]3-CsA blocks substrate access to CaN independent of CypA 1 μMa Baumgrass R 2004 [73]
FK506/FKBP12 complex blocks substrate access to the active centre of CaN 0.4 nMa Fruman DA 1992 [197]
Ascomycin/FKBP12 complex blocks substrate access to the active centre of CaN 0.7 nMm Sinclair PJ 1996 [198]
Pimecrolimus/FKBP12 complex blocks substrate access to the active centre of CaN 0.4 nMa Grassberger M 1999 [82]
Inhibitors of calcineurin-dependent signalling - alternative inhibitory compounds
1,5-dibenzoyloxymethyl-norcantharidin binds to the active centre of CaN 7 μMa Baba Y 2003 [101]
AM404 inhibits NFATc-DNA binding 10 μMc Caballero FJ 2007 [132]
BTP1 inhibits of NFATc dephosphorylation in cells 60 nMd Trevillyan JM 2001 [118]
BTP2 decreases Ca2+ influx into cytosol 10 nMc Ishikawa J 2003 [119]
Dibefurin inhibits enzymatic activity of CaN 44 μMe Brill GM 1996 [110]
Dipyridamole disrupts CaN-NFATc binding ~10 μMa Mulero C 2009 [111]
Gossypol inhibits enzymatic activity of CaN 17 μMa Baumgrass R 2001 [199]
INCA1   0.5 μM* f Roehrl MH 2004 [114]
INCA2 disturb CaN-NFATc complex formation by covalent binding to CaN 0.12 μM* f Roehrl MH 2004 [114]
INCA6   0.8 μM* f Roehrl MH 2004 [114]
Kaempferol inhibits enzymatic activity of CaN 51.3 μMa Wang H 2008 [94]
Lie120 inhibits enzymatic activity of CaN 5 μMa Klettner A 2001 [80]
NCI3 disturbs CaN-NFATc binding in cells 2 μMc Sieber M 2007 [113]
PD 144795 inhibits enzymatic activity of CaN ~3 μMa Gualberto A 1998 [109]
Roc-1 enhances rephosphorylation and nuclear export of NFATc 5~25 nMc Proksch P 2005 [136]
ST1959/DL111-IT enhances nuclear export of NFATc 13.5 μM Lindstedt R 2009 [128]
Thiopental inhibits CaM-dependent activity of CaN 0.18 mMa Humar M 2004 [97]
Trifluoperazine inhibits binding of CaM to CaN 8 μMg Aussel C 1995 [144]
Tropisetron inhibits CaN-dependent NFATc transactivation ~50 μMc Vega Lde L 2005 [138]
UR-1505 inhibits NFATc binding to DNA 100~300 μMh Román J 2007 [133]
WIN 53071 alters NFATc binding to DNA 3.4 μMh Baine Y 1995 [141]
Inhibitors of calcineurin-dependent signalling - unknown mode of action
Caffeic Acid Phenethyl Ester N.D. 0,1~1 μMc Marquez N 2003 [146]
KRM-III N.D. 5 μMc Jung EJ 2009 [145]
NFAT-68 N.D. 0.63 μMc Burres NS 1995 [152]
YM-53792 N.D. 50 nMc Kuromitsu S 1997 [149]
Punicalagin N.D. < 5 μMg Lee SI 2008 [153]
Imperatorin N.D. 37 μMc Marquez N 2004 [154]
Quinolone alkaloid compounds 1 and 3 N.D. 3.4 μMc Jin HZ 2004 [155]
Impressic acid N.D. 12.6 μMc Cai XF 2004 [159]
oleanane triterpenoid compound 3 N.D. 4.6 μMc Dat NT 2004 [162]
Gomisin N N.D. 1.33 μMc Lee IS 2003 [163]
  1. N.D.: not determined
  2. Indicated methods for IC50/Kd/Ki determination: a - phosphatase assay on RII phosphopeptide; b - phosphatase assay on pNPP; c - NFAT dependent reporter gene expression; d - IL-2 promoter dependent reporter gene expression; e - phosphatase assay on 4-methylumbelliferyl phosphate; f - displacement of VIVIT peptide; g - IL-2 secretion assay; h -EMSA for NFATc; i - interference with CaN-NFATc binding assay; k - binding assay to CaN; l - phosphatase assay on NFATc; m - cell proliferation assay