Table 1. Compound activity as determined in the luminescent SMFA compared to activities reported by published gametocyte viability assays and asexual replication assays.
| Compound | washout SMFA |
direct SMFA | published gametocyte assay data |
asexual blood stage† | |||||
|---|---|---|---|---|---|---|---|---|---|
| IC50 μM (95% CI) | slope (95% CI) | % inh. 10 μM | exflagellation12 (imaging) IC50 μM (% inh. 1 μM) | Pfs2512 IC50 μM (% inh. 1 μM) | alamarBlue24 IC50 μM (% inh. 5 μM) | imaging25 IC50 μM (% inh. 5 μM) | exflagellation26 (SYBR green) IC50 μM (% inh. 10 μM) | IC50 (μM) | |
| MMV000248 | 1.64 (1.26 − 2.13) | -2.44 (-3.07 − -1.81) | 48.76* | NA (-66%) | NA (8%) | 0.31 | 1.1 | NA (95%) | 0.72 |
| MMV000442 | 0.59 (.35 − 1.01) | -1.18 (-1.58 − -0.78) | 5.50 | NA (-12%) | NA (6%) | NA (72%) | 0.92 (55%) | NA (59%) | 0.36 |
| MMV000448 | 1.18 (1.07− 1.31) | -11.63 (-15.91 − -7.34) | 97.93* | 0.25 | 4.02 | 1 | 0.71 | 5.4 | 0.23 |
| MMV007116 | 0.11 (.06 − .19) | -1.62 (-2.15 − -1.08) | 99.22* | 20.75 | NA (10%) | NA (40%) | 0.26 | NA (67%) | 0.35 |
| MMV011438 | 8.58 (7.95 − 9.26) | -8.47 (-12.62 − -4.32) | -3.29 | NA (-77%) | NA (-31%) | 0.82 | 1.13 | NA (69%) | 0.32 |
| MMV019266 | 1.29 (1.21 − 1.38) | -9.38 (-12.41 − -6.35) | 7.07 | NA (31%) | NA (-11%) | 0.31 | 0.33 | NA (81%) | 0.62 |
| MMV019881 | 1.17 (. −.) | -15.81 (. −.) | 88.15* | NA (57%) | NA (-7%) | NA (76%) | NA (32%) | 5.5 | 0.65 |
| MMV019918 | 0.07 (.04 − .13) | -1.36 (-1.80 − -0.93) | 88.55* | 0.07 | 0.52 | 0.32 | 0.7 | 0.9 | 0.79 |
| MMV020492 | ND | ND | -16.63 | NA (36%) | NA (-12%) | NA (70%) | NA (-5%) | NA (59%) | 0.03 |
| MMV396797 | 3.62 (.87 − 15.18) | -4.10 (-9.87 − 1.67) | -16.44 | NA (-14%) | NA (-17%) | NA (90%) | 0.01 | 8.8 | 0.48 |
| MMV665827 | 0.10 (.06 −.15) | -2.23 (-3.05 − -1.42) | 98.25* | 16.55 | NA (-15%) | NA (41%) | 0.34 | NA (66%) | 0.12 |
| MMV665882 | ND | ND | 4.92 | NA (-12%) | NA (-48%) | NA (92%) | 0.07 | NA (75%) | 0.47 |
| MMV665941 | 0.04 (. − .) | -10.29 (. − .) | 99.84* | 0.42 | 0.3 | NA (86%) | 0.32 | 1.8 | 0.26 |
| MMV665971 | 3.22 (1.45 − 7.15) | -1.50 (-2.57 − -0.44) | -7.04 | NA (–29%) | NA (–13%) | NA (73%) | 0.23 | NA (61%) | 0.49 |
| MMV665980 | 1.76 (1.57 − 1.96) | -11.52 (-25.29 − 2.24) | 64.17* | 8.07 | NA (74%) | NA (27%) | NA (91%) | NA (76%) | 0.21 |
| MMV666021 | 1.25 (1.17 − 1.34) | -13.30 (-17.32 − -9.28) | 94.02* | NA (30%) | NA (–20%) | NA (58%) | 0.61 | NA (68%) | 0.09 |
| MMV666125 | 1.40 (1.11 − 1.76) | -2.86 (-3.97 − -1.76) | -24.69 | NA (–3%) | NA (–17%) | 0.48 | 0.75 | NA (74%) | 0.38 |
| MMV667491 | 0.06 (.03 − .11) | -0.61 (-0.73 − -0.50) | 89.05* | 0.09 | 0.18 | NA (91%) | 1.06 | 4.5 | 1.23 |
The table shows IC50 values where available (NA: not available) or the percentage inhibition at the highest concentration tested, as indicated in the header row. IC50 data for the exflagellation (imaging) and Pfs25 assays were generated in a washout format, whereas percentage inhibition values represent data from a continued exposure experiment12. For SMFA data, 95% confidence intervals are indicated between brackets where possible. For MMV019881, and MMV665941 the model did not converge. Asterisks (*) indicate statistically significant inhibition (p < 0.05) in the direct SMFA. † The last column shows activity against asexual blood stages of P. falciparum strain 3D7 as deposited at the ChEMBL repository under accession number CHEMBL2028071. ND: no dose response relationship was detected in the data.