TABLE 2

Bidirectional flux studies using MDCK cell monolayers that overexpress human P-gp

Inhibition with 2.5 μM LSN335984. Average values are from duplicate test runs where variability is <22%.

Compound	Inhibitor	A-B P_app	B-A P_app	%Cell^{^a}	ER^{^b}	NER^{^b}	Calcein-AM Inhibition^{^c}
		nm/s					%
Abemaciclib	−	12	49	68	4.1	5.1	30, 64
	+	19	16	56	0.8
Palbociclib	−	60	720	46	12	8.6	1, 3
	+	150	210	32	1.4

A-B, apical to basal; B-A, basal to apical; ER, efflux ratio; NER, net efflux ratio.
↵^a Estimated buffer/cell distribution coefficient defined as the fraction of mass that was added to the donor and recovered in the methanol rinse.
↵^b ER is B-A P_app/A-B P_app. NER is ER without inhibitor/ER with inhibitor.
↵^c Inhibition of Calcein-AM uptake into MDCK–P-gp cells at 5 and 25 μM relative to inhibition using 5 μM LSN335984.