. 2022 May 23;13(6):981–988. doi: 10.1021/acsmedchemlett.2c00116

Table 3. In Vitro ADME Profile Comparisons of Select 1H-Pyrazole-based GS-LRRK2 Inhibitors^a.

entry	GS IC₅₀ / nM^a	IC₅₀ ratio	WT EC₅₀ / μM^a	GS EC₅₀ / μM^a	EC₅₀ ratio	Caco-2		efflux Ratio	MLM^c	HLM^c	TPSA^d/ Å²	kinase profile^f
entry	GS IC₅₀ / nM^a	IC₅₀ ratio	WT EC₅₀ / μM^a	GS EC₅₀ / μM^a	EC₅₀ ratio	A-B^b	B-A^b	efflux Ratio	MLM^c	HLM^c	TPSA^d/ Å²	kinase profile^f
13	15.5	16.3	76	1.5	51	7.14	30.4	4.3	7.4	28	114.2	n.t.
7	21.3	4.8	>100	2.1	48	10.3	38.9	3.8	28	140	101.7	n.t.
19	1.1	7.5	>100	0.29	345	4.21	40.6	9.6	1.6	57	114.2	n.t.
30	2.2	8.9	>100	0.26	385	4.27	40.5	9.5	19	119	101.7	n.t.
37	3.1	8.3	>100	0.39	256	8.78	27.0	3.1	30	159	101.7	12 (6)
41	2.4	7.1	5.4^e	0.28	19.3	3.36	25.7	7.6	9.9	102	101.7	12 (6)

See footnotes for Table 1. “n.t.” = not tested.

P_app (× 1 e^–6 cm/s).

t_1/2 (min).

Calculated at pH 7.4.

34% activity remaining at 30 μM.

Number of kinases inhibited at >80% out of a total of 485 kinases (0.1 μM inhibitor). Kinases inhibited other than LRRK2 variants in parentheses (see Figures S1, S2).

Table 3. In Vitro ADME Profile Comparisons of Select 1H-Pyrazole-based GS-LRRK2 Inhibitorsa.

Table 3. In Vitro ADME Profile Comparisons of Select 1H-Pyrazole-based GS-LRRK2 Inhibitors^a.