Immunosuppressive properties of the FK520 analogs
| Compound | Kd | IC50 | ||
|---|---|---|---|---|
| FKBP12 Binding | FKBP52 Binding2-a | Calcineurin Inhibition2-b | T-Cell Suppression2-c2-e | |
| nM | nM | |||
| FK506 | 0.4 ± 0.1 | 82 | 25 | 0.35 |
| FK520 | 0.5 ± 0.1 | 35 | 49 | 3.9 ± 2.7 |
| 13-H FK520 | 0.6 ± 0.3 | 120 | 32 | 8.7 ± 3 |
| 13-Me FK520 | 0.9 ± 0.6 | 130 | 940 | >10,0002-d |
| 13-H-15-H FK520 | 0.5 ± 0.3 | N.D. | 8,600 | 10,000 |
| 13-H-15-Me FK520 | 3.2 ± 1.6 | 340 | 8,200 | N.D. |
| 13-H-15-Et FK520 | 4.1 ± 2.2 | 290 | 10,000 | 6302-e |
| 13-Me-18-OH FK520 | 0.2 ± 0.1 | 86 | >10,000 | >10,0002-d |
N.D., not determined.
↵2-a Values are from one determination.
↵2-b Values were ±10%.
↵2-c IC50 values of compounds in concanavalin A stimulated T-cell proliferation assay.
↵2-d No immunosuppressive activity was detected at 10 μM.
↵2-e No toxic effects towards T cells were observed when compounds were tested up to 100 nM using the XTT assay for cell viability, except 13-H-15-Et FK520, IC50 = 2500 nM.