TABLE 5.
Cytotoxicity and cardiotoxicity data for UCT943 and MMV048a
| Toxicity in cell line or ion channel | CC50 (SI), μMb |
UCT943 lowest SIc | |
|---|---|---|---|
| MMV048 | UCT943 | ||
| Cytotoxicity | |||
| CHO cells | 17 (3,148) | 298 | |
| Vero cells | 113 (20,926) | 1,982 | |
| HepG2 cells | >10 (357) | 13 (2,407) | 225 |
| L6 cells | 251 (8,964) | 12 (2,222) | 211 |
| Cardiotoxicity | |||
| hERG (Kv11.1) | >11 (393) | 10 [6.4–15.9] (1,870) | 177 |
| NaV1.5 | 100 (3,571) | >33 (>6,111) | >579 |
| CaV1.2 | 16 (571) | >33 (>6,111) | >579 |
| KV1.5 | >33 (>6,111) | >579 | |
a
Both MMV048 and UCT943 were negative for genotoxicity by the Ames test and micronucleus assay.
b
CC50, 50% cytotoxic concentration; SI, selectivity index. SI is calculated as the CC50/IC50 of strain NF54, where IC50 is the 50% inhibitory concentration. SI values are given as fold change.
c
Lowest selectivity index against clinical isolates. The lowest SI is calculated as the CC50/maximum IC50 of the P. falciparum clinical isolates.