Table 1.
Protein-knockdown activities and binding affinities of SNIPER(ER)s
| Compound no. | ERα DC50 |
IC50 (95% CI) |
IAP ligand |
|||||
|---|---|---|---|---|---|---|---|---|
| 4 h | 48 h | ERα | cIAP1 | cIAP2 | XIAP | Originator | Reference | |
| nm | nm | |||||||
| SNIPER(ER)-87 | <3 | 83.0 | 110 (58–200) | 450 (360–560) | 960 (600–1500) | 700 (510–960) | Novartis | WO2008016893 |
| SNIPER(ER)-104 | >100 | NDa | 61 (26–140) | >1000 | >1000 | >1000 | Novartis | WO2012080260 |
| SNIPER(ER)-105 | <3 | <3 | 69 (7–670) | 5.3 (4.6–6.1) | 7.2 (4.9–11) | 55 (38–80) | Novartis | WO2012080271 |
| SNIPER(ER)-110 | <3 | 7.7 | 120 (68–200) | 74 (62–89) | 73 (55–97) | 330 (250–430) | Abbott | Ref. 52; WO2016169989 |
| SNIPER(ER)-113 | <3 | 13.3 | 150 (82–290) | 85 (75–96) | 99 (58–200) | 810 (58–200) | Abbott | Ref. 52; WO2016169989 |
| SNIPER(ER)-118 | >100 | ND | 230 (73–540) | 140 (58–200) | 900 (58–200) | >1000 | AstraZeneca | Ref. 53 |
| SNIPER(ER)-119 | 4 | 15.7 | 200 (73–540) | 80 (62–100) | 48 (28–82) | 700 (490–1000) | Abbott | Ref. 52; WO2016169989 |
| SNIPER(ER)-121 | >100 | ND | ND | 650 (540–780) | >1000 | >1000 | AstraZeneca | Ref. 53 |
| SNIPER(ER)-126 | <3 | 3.7 | 83 (2–3800) | 68 (66–77) | 200 (150–280) | 490 (310–760) | Novartis | WO2008016893 |
| SNIPER(ER)-130 | 36.9 | ND | 41 (25–65) | 68 (60–77) | 28 (21–39) | 25 (17–37) | Genentech | Ref. 54 |
| SNIPER(ER)-131 | 33.8 | ND | 80 (39–160) | 25 (22–28) | 24 (18–32) | 140 (85–220) | Genentech | Ref. 55 |
| SNIPER(ER)-134 | >100 | ND | 47 (15–140) | 550 (450–670) | 360 (240–540) | >1000 | Abbott | Ref. 52 |
| SNIPER(ER)-136 | >100 | ND | 47 (25–89) | 890 (790–1000) | >1000 | >1000 | Genentech | Ref. 54; WO2006069063 |
a ND, not determined.