Table 2.
Biochemical characterization of PPIase inhibitor compounds.
| Name | In vitro Inhibition human CypA IC50 [nM] | In vitro Inhibition CnA IC50 [μM] | In vitro inhibition NFAT reporter gene assay IC50 [μM] | NFAT-GFP Translocation in HEK- 293 cells | Inhibition of HCoV-NL63 in CaCo-2 EC50 [μM] |
|---|---|---|---|---|---|
| CsA | 9.1 ± 0.8 | 0.05 | 1.6 ± 0.0003 | no | 0.9–2.0 |
| CsD | nd | nd | nd | no | 2.5 |
| ALV | nd | nd | nd | yes | 0.8 |
| NIM811 | nd | nd | nd | yes | 0.8 |
| 1 | 9.1 ± 1.4 | no | no | yes | 1.6 |
| 2 | 57.5 ± 6.9 | no | no | yes | 7.9 |
| 3 | 11.9 ± 0.9 | 6.9 | 45% at 10 μM | yes | 1.1 |
| 4 | 14.1 ± 1.9 | ∼10 | 1.3 | yes | 8.1 |
| 5 | 16.6 ± 2.3 | >10 | 1.2 | yes | 2.3 |
| FK506 | nd | nd | nd | no | 6.6 |
| 6 | 10.2 ± 1.9* | no | no | yes | 4.2 |
Properties of CsA (compounds 1–5) and FK506 (compound 6) analogues with respect to inhibition of PPIA in a protease-coupled PPIase assay, FKBP12 inhibition (*), CaN, NFAT, and NFAT-GFP nuclear translocation. Methods are described in Prell et al. (2013). The last column represents the EC50 inhibitory values of the peptides on HCoV-NL63 infection of Caco-2 cells.