Cell penetration and passive membrane permeability of Odz macrocycles as measured by CAPA and PAMPA, and relative hydrophobicity as measured by reverse-phase HPLC.
| Compounds | CP50 after 30 min incubationa (μM) | CP50 after 4 h incubationa (μM) | −log Peb | T ret c (min) |
|---|---|---|---|---|
| 1 | 0.028 ± 0.002 | 0.0090 ± 0.0006 | 7.77 ± 0.02 | 8.87 |
| 2 | 12.8 ± 2.4 | 2.2 ± 0.1 | 7.92 ± 0.07 | 8.00 |
| 3 | 0.48 ± 0.02 | 0.16 ± 0.01 | 7.84 ± 0.04 | 8.92 |
| 4 | 0.085 ± 0.005 | 0.028 ± 0.001 | 7.85 ± 0.052 | 8.63 |
| 5 | 0.51 ± 0.04 | 0.12 ± 0.003 | >8 | 7.82 |
| 6 | 4.5 ± 0.6 | 1.3 ± 0.1 | >8 | 8.70 |
| 7 | 9.0 ± 1.2 | 2.3 ± 0.2 | >8 | 7.88 |
| 8 | 1.0 ± 0.03 | 0.22 ± 0.02 | >8 | 7.95 |
| ct-W | 0.25 ± 0.01 | 0.028 ± 0.001 | — | — |
| ct-R9W | 2.18 ± 0.45 | 0.56 ± 0.07 | — | — |
a
CAPA results were determined by incubating ct-peptides with cells in Opti-MEM for 30 min or 4 h prior to chasing with ct-dye.
b
−log Papp values were determined using PAMPA with carbamazepine as an internal standard.
c
Retention time values were determined using C18 LC-MS, gradient 95%/5% MeCN to 100% MeCN over 15 min. Errors represent standard error of the mean from three independent trials.