High-Throughput, Non-Electrophysiological Screening for Drug-Induced Trafficking Risk
System: CHAN-Lite® is a proprietary cell-based ELISA that monitors the surface expression of ion channels. Stable HEK293 cell lines overexpressing individual wild-type channels are incubated with test compounds overnight. Results are reported as relative surface expression and compared to channel-specific positive controls.
Benefits:
- Identify potential trafficking risks early with CHAN-Lite®, the only high-throughput, cost-effective assay for measuring drug-induced trafficking risk; don’t wait until costly in vivo studies suggest trafficking problems!
- Determine specificity of drug-induced trafficking inhibition with CHAN-Lite®
- Identify compounds that enhance cell surface expression with CHAN-Lite®
- Rapid results (two week turnaround) with CHAN-Lite®
| relative surface expression | ||||||
| channel | geldanamycin (1 mM) |
arsenic trioxide (10 mM) |
pentamidine (30 mM) |
digitoxin (30 nM) |
ivermectin (3 mM) |
brefeldin A (1 mM) |
| hERG | 0.50 |
0.35 |
0.44 |
0.33 |
0.55 |
0.50 |
| Kv1.5 | NC |
NC |
NC |
NC |
0.51 |
0.67 |
| Kv4.3 | 2.44 |
NC |
NC |
NC |
0.39 |
0.44 |
| KvLQT1-minK | NC |
NC |
NC |
0.26 |
0.59 |
0.41 |
| Kir2.1 | NC |
2.39 |
NC |
NC |
NC |
0.53 |
SPECIFICITY OF DRUG-INDUCED TRAFFICKING INHIBITION :
Six hERG trafficking inhibitors were examined for their effects on relative surface expression of four other cardiac ion channels. CHAN-Lite® detects both increases (yellow highlights) and decreases (pink highlights) in channel surface expression. NC indicates no significant change from vehicle control. Brefeldin A blocks endoplasmic reticulum to Golgi transport and is a nonspecific trafficking inhibitor.
