Table 3.

Summary of key antimalarials, front-runner and development compounds as well as investigative hits with in vitro activity (>70% inhibition, or < 5 µM IC₅₀) against male and female gametes, as well as oocyst formation.

Compound	Gametes (%) a		TRA% b	Target	Ref
	Male	Female
Chlorproguanil	–	–	100	DNA replication/ transcription	(Vos et al., 2015)
Cycloguanil	96	0			(Delves et al., 2013)
P218	4*	–	99		(Vos et al., 2015; Posayapisit et al., 2021)
Pyrimethamine	94	0	100		(Delves et al., 2013; Vos et al., 2015)
Atovaquone	12	12	100	Cytochrome bc1 (Qo)	(Delves et al., 2013; Vos et al., 2015)
ELQ-300			100	Cytochrome bc1 (Qi)	(Nilsen et al., 2013)
Cycloheximide	100#	–	100	Unknown	(Vos et al., 2015)
KDU691	–	–	100	PfPI4K	(Mcnamara et al., 2013)
MMV390048	90*	–	69		(Paquet et al., 2017)
AZD-0156	84&		65&		(Reader et al., 2021)
M5717 (DDD498)	–	–	1.8*	PfEF2	(Baragana et al., 2015)
GNF179	–	–	100	Protein secretory pathway	(Plouffe et al., 2016)
Ganaplacide (KAF156)	–	–	90		(Kuhen et al., 2014)
ML324	93&	–	95&	PfJmj3	(Reader et al., 2021)
JIB-04	10	80	–		(Matthews et al., 2020)
ML10	–	–	41*	PfPKG	(Baker et al., 2017)
MMV030084	141*	0	–		(Vanaerschot et al., 2020)
Methylene blue	98	11	99	Glutathione reductase	(Delves et al., 2013; Vos et al., 2015)
Epoxomicin	–	–	100	β2 and 5 subunits of the proteasome	(Czesny et al., 2009)
BIX01294	120*	727*	–	HKMT	(Malmquist et al., 2015)
SJ733			5mg/kg@	PfATP4	(Dechering et al., 2017)
KAE609 (NITD609)			100		(Van Pelt-Koops et al., 2012)
Birinapant	75&		78&	Caspase 3	(Reader et al., 2021)
MMV1581558	79&		80&	Unknown (Adenosine A3 receptor)
MMV1580843	70&		84&	Unknown
SQ109	53&		80&	Unknown (MmpL3 in Mtb)
TCMDC-137173	76	21	25*	Unknown	(Delves et al., 2019)
TCMDC-134114	99	0	56*
DDD01035881	540*	>10*		Pfs16	(Delves et al., 2018b; Yahiya et al., 2021)
DDD01028074	220*	>10*		Unknown	(Delves et al., 2018b)

^a% inhibition at 1 µM.

^bTRA: transmission-reducing activity at 5 µM.

* IC₅₀ (nM).

# % inhibition at 10 µM.

^& Inhibition of gamete formation at 2 µM.

^@ ED₅₀ in P. berghei.