. Author manuscript; available in PMC: 2021 Nov 3.

Published in final edited form as: Int J Parasitol. 2020 Mar 26;50(5):413–422. doi: 10.1016/j.ijpara.2020.01.006

Table 1.

Activity of chiral and non-chiral Bumped Kinase Inhibitors (BKIs)

BKI	Scaffold	Chiral	R2 substituent	TgCDPK1 IC₅₀ (μM)	Toxoplasma gondii EC₅₀ (μM)	CpCDPK1 IC₅₀ (μM)	Cryptosporidium parvum EC₅₀ (μM)	C. parvum efficacious dose in mouse^a
1634	AC	X	oxolane	0.0060		0.0026	1.183	60 mg/kg QD
1841	AC		oxane	0.0301	0.13	0.0028	1.21
1842	AC		oxane	0.0376	0.17	0.0045	0.26
1712	AC	X	4-hydroxybutan-2-yl	0.0159	0.367	0.0059	0.599
1713	AC	X	4-hydroxybutan-2-yl	0.0169	0.472	0.0169	0.472	60 mg/kg QD
1768	AC	X	4-hydroxybutan-2-yl	0.0002	0.128	0.0020	0.374	60 mg/kg QD
1769	AC	X	4-hydroxybutan-2-yl	0.0005	0.343	0.0020	0.43
1745	AC		4-hydroxy-2-methylbutan-2-yl	0.0030	0.366	0.0040	0.25	15 mg/kg QD
1770	AC		4-hydroxy-2-methylbutan-2-yl	0.0002	0.147	0.0025	0.344	30 mg/kg BID

Efficacious dose results in >2 log unit reduction in oocyst shedding after 5 days of treatment.

IC₅₀, inhibitory concentration that leads to a 50% reduction; EC₅₀, effective concentration that leads to a 50% reduction in growth; QD, once daily; BID, twice daily; AC, 5-aminopyrazole-4-carboxamide.