Source Name: 2021_Comeau
Literature Information
| Literature Title | Modulation of the Passive Permeability of Semipeptidic Macrocycles: N- and C-Methylations Fine-Tune Conformation and Properties |
| Doi | 10.1021/acs.jmedchem.0c02036 |
| Research Group |
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| Data Number | 42 |
| Minimum Molecular Weight | 430.5 |
| Maximum Molecular Weight | 458.6 |
Assay Information 1
| Assay Type | PAMPA |
| Permeability Type | logPe |
| Membrane Measurement Direction (Exclude PAMPA) | - |
| Assay Detail | Passive permeability assays were run in triplicate on 96-well hydrophobic poly(vinylidene difluoride)(PVDF)plates (Millipore, 0.45 μM, 200 μL) and 300 μL receptor plates (Millipore). Assays were carried out using a 10 μL membrane (2% lecithin in dodecane) with a 100 μMsolution in a phosphate buffer (pH = 6.4) and shaken for 17 h (25 °C, 50 rpm). |
Assay Information 2
| Assay Type | Caco2 |
| Permeability Type | logPapp |
| Membrane Measurement Direction (Exclude PAMPA) | Average of Apical to Basolateral (AB) and Basolateral to Apical (BA) |
| Assay Detail | Assays were run in triplicate on polycarbonate Transwell plates (Corning) with hydrophilic filters (0.45 μM, Millipore). Caco-2 cells were passaged >72 times and grown on the filter for 22 days, at which point the transepithelial electrical resistance (TEER) was over 300 Ω cm^2. Compounds were tested in an initial 10 μM solution using an Hank's balanced salt solution (HBSS) buffer (N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid (HEPES)/NaOH, pH = 7.4) and a sample was taken after 60 and 120 min at 37 °C. Propranolol and atenolol were used as control compounds for high and low permeabilities, respectively. The assays were performed in both apical-to-basolateral and basolateral-to-apical directions to better assess the effect of efflux. |