| Description | Cercosporamide is a ATP-competitive Pkc1 kinase inhibitor (IC50 <50 nM; Ki <7 nM). It also is a unique Mnk inhibitor. |
| In vitro | Cercosporamide is a broad-spectrum natural antifungal compound and a selective and highly potent fungal Pkc1 kinase inhibitor [1]. Cercosporamide is recently shown to act as a unique Mnk inhibitor with antileukemic properties. Cercosporamide is a potent inhibitor of phosphorylation of eIF4E at Ser209 in AML cells and results in potent inhibitory effects on primitive leukemic progenitors (CFU-L) from AML patients. When U937 cells are incubated in the presence or absence of the increasing doses of Cercosporamide, dose-dependent suppression of cell growth is found. Similar experiments with comparable results are seen when the effects of Cercosporamide on MM6 and K562 cells are examined [2]. |
| In vivo | Treatment with Cercosporamide or Ara-C alone significantly suppresses xenograft growth when compared with the respective vehicle (P<0.011 for 10 mg/kg twice-daily Cercosporamide; P<0.006 for Cercosporamide 20 mg/kg daily; P<0.0374 for Ara-C). The combination of Cercosporamide 10 mg/kg twice daily plus Ara-C is significantly more effective than either agent alone. Cercosporamide (20 mg/kg once daily) in combination with Ara-C shows similar effects, with significant inhibition of tumor growth vs captisol (P<0.0001) or water (P=0.0003), but does not show statistical significance vs Cercosporamide alone (20 mg/kg) or Ara-C alone [2]. |
| Target activity | MNK:50 nM, PKC1:50 nM, PKC1:7 nM (ki) |
| Synonyms | (-)-Cercosporamide |
| molecular weight | 331.28 |
| Molecular formula | C16H13NO7 |
| CAS | 131436-22-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Sussman A, et al. Discovery of Cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high-throughput screening. Eukaryot Cell. 2004 Aug;3(4):932-43. 2. Altman JK, et al. Inhibition of Mnk kinase activity by Cercosporamide and suppressive effects on acute myeloid leukemia precursors. Blood. 2013 May 2;121(18):3675-81. |