Basic Information
ID: ALA3887143
Type: Binding
Description: IDE Activity Assay: Macrocycles were assayed for IDE inhibition by monitoring cleavage of a substrate peptide containing a fluorophore-quencher pair such that cleavage of the model substrate results in increased fluorescence. Although our selection did not explicitly select for inhibition (only binding is required for enrichment), all four strongly enriched macrocycles inhibited IDE activity with IC50<10uM or equal to 10uM. The most potent macrocycle, trans-A12-B8-C6-D5 (6b), inhibited IDE with an IC50 of 140 nM. The three-dimensional conformation adopted by these compounds appears to be important to their inhibitory activity, as the trans-olefin isomers of macrocycles 3, 5, and 6 exhibit >10-fold stronger potency than the corresponding cis-olefin macrocycle isomers (Table 1). Compounds 1 and 4, which contained glycine (A2) instead of D-benzoylphenylalanine (A12) at the A position were inactive against IDE.
Organism: Homo sapiens
Activity Charts
Bioactivity
Activity Types for Assay ALA3887143
IC50
Compound Summary
| Parent Molecular Weight | ALogP | Polar Surface Area |
|---|---|---|
| 1230.54 | ||
| 844.03 | 0.85 | 0.85 |
| 830.00 | 0.46 | 0.46 |
| 1277.44 | ||
| 691.79 | -0.35 | -0.35 |
| 832.96 | 1.68 | 1.68 |
| 845.01 | 1.45 | 1.45 |
| 858.05 | 1.11 | 1.11 |
| 717.82 | 0.20 | 0.20 |
| 740.90 | 2.51 | 2.51 |
| 757.89 | 0.98 | 0.98 |
| 716.84 | 0.70 | 0.70 |
| 632.80 | 0.59 | 0.59 |
| 758.87 | 1.58 | 1.58 |
| 686.81 | 1.34 | 1.34 |
| 700.84 | 1.73 | 1.73 |
| 700.84 | 1.73 | 1.73 |
| 717.82 | 0.05 | 0.05 |
| 757.93 | 1.84 | 1.84 |
| 563.66 | -1.87 | -1.87 |
| 827.04 | 3.43 | 3.43 |
| 672.78 | 1.94 | 1.94 |
| 751.84 | 0.25 | 0.25 |
| 776.94 | 2.95 | 2.95 |
| 653.78 | -0.25 | -0.25 |
| 714.86 | 2.12 | 2.12 |
| 757.89 | 0.98 | 0.98 |
| 785.95 | 0.97 | 0.97 |