sst2, sst3, and sst5 Binding Affinities and Internalization of Somatostatin and Somatostatin Analogs
| Receptor internalization | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Binding affinity | sst2 | sst3 | sst5 | ||||||
| Compound | sst2 | sst3 | sst5 | HEK* | CHO† | Antagonized | HEK* | Antagonized | HEK* |
| Natural somatostatins | |||||||||
| Somatostatin-28 | 2.3 ± 0.1 (39) | 3.7 ± 0.3 (38) | 2.4 ± 0.2 (36) | + | + (0.71 ± 0.05) | Yes | + | Yes | + |
| Somatostatin-14 | 0.7 ± 0.2 (5) | 3.3 ± 1.7 (4) | 10 ± 4 (4) | + | ND | Yes | + | ND | + |
| Various synthetic analogs | |||||||||
| [Tyr3]-octreotide (TOC) | 2.8 ± 0.6 (4) | 225 ± 82 (4) | 9.9 ± 1.8 (4) | + | + (0.51 ± 0.07) | Yes | − | ND | − |
| Vapreotide acetate (RC160) | 1.8 ± 0.3 (5) | 233 ± 34 (4) | 4.8 ± 0.9 (5) | + | + (4.3 ± 1.4) | ND | − | ND | − |
| Lanreotide (BIM-23014) | 1.6 ± 0.4 (2) | 438 ± 39 (2) | 7.4 ± 1.2 (2) | + | + (1.6 ± 0.1) | ND | − | ND | − |
| KE108 | 0.9 ± 0.1 (7) | 1.5 ± 0.2 (7) | 0.7 ± 0.1 (7) | + | ND | Yes | + | Yes | − |
| NOC-ATE | 3.6 ± 1.6 (3) | 302 ± 137 (3) | 17 ± 10 (3) | + | ND | ND | − | ND | − |
| BIM-23244 | 0.18 ± 0.02 (3) | 53 ± 7 (3) | 0.5 ± 0.2 (3) | + | + (0.08 ± 0.01) | ND | − | ND | − |
| L-779,976 | 0.6 ± 0.1 (4) | >1,000 (4) | >1,000 (4) | + | + (0.73 ± 0.18) | ND | − | ND | − |
| L-817,818 | >1,000 (3) | 164 ± 17 (2) | 1.6 ± 0.4 (4) | − | — | ND | − | ND | − |
| Chelated analogs | |||||||||
| DTPA-octreotide (MP2321) | 13 ± 2 (5) | 376 ± 84 (5) | 299 ± 51 (6) | + | + (23 ± 1) | Yes | − | ND | − |
| DOTA-lanreotide (MP2353) | 26 ± 3 (6) | 771 ± 229 (6) | 73 ± 12 (6) | + | + (4.5 ± 0.4) | Yes | − | ND | − |
| Y-DOTA-TOC | 11 ± 2 (6) | 389 ± 135 (5) | 114 ± 29 (5) | + | + (0.72 ± 0.14) | Yes | − | ND | − |
| Y-DOTA-lanreotide | 23 ± 5 (4) | 290 ± 105 (4) | 16 ± 3 (4) | + | ND | Yes | − | ND | − |
| Y-DOTA-NOC | 3.3 ± 0.2 (3) | 26 ± 2 (3) | 10 ± 2 (3) | + | + (0.41 ± 0.01) | Yes | + | Yes | − |
| Y-DOTA-TATE | 1.6 ± 0.4 (3) | >1,000 (3) | 187 ± 50 (3) | + | + (0.61 ± 0.08) | Yes | − | ND | − |
| Lu-DOTA-BOC-ATE | 2.4 ± 0.3 (2) | 11 ± 1 (2) | 8.3 ± 0.4 (2) | + | + (0.46 ± 0.11) | Yes | + | ND | − |
| Lu-DOTA-NOC-ATE | 3.6 ± 0.3 (2) | 31 ± 2 (2) | 15 ± 1 (2) | + | + (1.0 ± 0.3) | Yes | + | ND | − |
| I-Gluc/Gal-compounds | |||||||||
| I-Gluc-TOC | 2.2 ± 0.7 (3) | 357 ± 22 (3) | 64 ± 24 (3) | + | + (0.78 ± 0.12) | Yes | − | ND | − |
| I-Gluc-TATE | 2.0 ± 0.5 (3) | >1,000 (3) | 521 ± 269 (3) | + | ND | Yes | − | ND | − |
| I-Gluc-S-TATE | 2.0 ± 0.7 (3) | 398 ± 19 (3) | 310 ± 156 (3) | + | + (0.73 ± 0.21) | Yes | − | ND | − |
| I-Gal-S-TATE | 2.0 ± 0.8 (3) | 491 ± 63 (3) | 413 ± 167 (3) | + | + (0.89 ± 0.31) | Yes | − | ND | − |
| Antagonists | |||||||||
| Coy-14 (BIM-23A760) | 10 ± 4 (4) | 61 ± 14 (3) | 53 ± 19 (2) | — | — | ND | ND | ND | ND |
| sst3-ODN-8 | >1,000 (3) | 6.7 ± 2.6 (3) | >1,000 (3) | ND | ND | ND | − | ND | ND |
↵* For immunofluorescent internalization assay in HEK cells, + = internalized at agonist dose of at least 100 nmol/L, − = not internalized at agonist dose of greater than 100 nmol/L, and ND = not determined.
↵† For internalization measured with ELISA in CHO-sst2 cells, + = internalized, − = not internalized, and ND = not determined. Values in parentheses are median effective concentration, EC50 (±SEM, n ≥ 2).
Binding affinities were measured using in vitro receptor autoradiography, as reported previously. Values were taken from previous reports (4,18,25–27,38,39) or represent our unpublished data. Binding affinity values are inhibitory concentration of 50% (IC50), in nmol/L (mean ± SEM); number of independent studies is given in parentheses. Antagonized means abolition of receptor internalization in presence of excess concentrations of receptor-specific antagonist, either Coy-14 for sst2 or sst3-ODN-8 for sst3, performed with immunofluorescent internalization assay in HEK-sst2 or HEK-sst3 cells.