TABLE 1.

Top 12 molecules exhibiting late-stage schizont inhibition^a

Pathogen Box identifier	Chemical class	EC50 value (μM)b	R50 value (μM)b	Trophozoite inhibition (%) at 1 μM	Schizont inhibition (%) at 1 μM	DNA damage (%) at 5 μM	Toxoplasma ionophore egress time (min) at 10 μMd	Function and possible targets [reference(s)]
MMV024443	Indole derivatives	1.66	0.306	NAc	58.6	30	7.00	CDPK1 (calcium-dependent protein kinase 1) lactate dehydrogenase (39–41)
MMV020623	Indole derivatives	0.22	0.414	14.15	70.6	30–40	4.10	PfATP4 dysregulation affecting Na+ efflux (41)
MMV010576	Pyridine and derivatives	0.19	0.138	20.57	60.4	30	6.50	Phosphatidylinositol 4-kinase (PI4K) activity (8), based on the elucidated target for clinical candidate MMV390048
MMV020520	Benzoxazines	0.22	0.432	35.84	84.6	30	3.30	PfATP4 dysregulation affecting Na+ efflux (41)
MMV085071	Indole derivatives	0.03	0.470	36.89	47.2	30	6.50	Rapid parasiticidal effect and programmed cell death (PCD)-like phenotypes (12)
MMV020670	6-Naphthyridine-2-carboxamide	1.56	0.787	37.03	64	>50	7.00	NA
MMV020081	Benzene and substituted derivatives	0.07	0.089	38.23	43.4	30	7.00	PfATP4 dysregulation affecting Na+ efflux (41)
MMV026356	2-Methylpyrazole-3-carboxamide	1.70	0.156	40.27	61.4	>50	7.00	NA
MMV006239	Alkaloid derivatives	0.16	0.495	42.32	90	25–30	7.00	NA
MMV020710	Azoles	0.06	0.241	43.63	84	25–30	7.00	PfATP4 dysregulation affecting Na+ efflux (41)
MMV020391	Benzene and substituted derivatives	0.11	0.132	44.04	90.4	25–30	NA	PfATP4 dysregulation affecting Na+ efflux (41)
MMV675968	Diazanaphthalenes	0.07	0.083	77.48	41.6	25–30	NA	Inhibits dihydrofolate reductase (Toxoplasma and Cryptosporidium) (11)

^aThe table lists 12 schizont inhibitors, their chemical class, consolidated study results, and their predicted mechanism of action.

^bData are from this study

^cNA, not available.

^dEgress was monitored up to a maximum of 7 min.