TABLE 2

BCRP substrate in vitro results of drugs tested in M-BCRP cells at 1 µM

When P_appAB could not be estimated as associated samples were below the limit of quantification, a value was calculated using the limit of detection and is indicated as “<” to this value; equally, the ER is estimated to be “>” to the calculated ratio. Ten more compounds were tested but failed in this high-throughput screening setup due to an apparent low permeability (all samples below the limit of detection, mostly corresponding to an average P_appi < 15 nm/s): doxorubicin, E3S, vincristine, lamivudine, MTX, rosuvastatin, metformin, tamoxifen, nitrofurantoin, sulfasalazine.

Compound Name	M-BCRP Cells Data										MDCKII Cells Data
Compound Name	Mean P_app AB	S.D.	Mean P_app BA	S.D.	M-BCRP ER	S.D.	Average P_appi	S.D.	ERi	S.D.	MDCKII ER	S.D.	Average P_app	S.D.	BCRP Substrate
FTC	253	11	246	49	1.0	0.2	234	40	1.4	0.1	1.0	0.2	294	48	N
Verapamil	197	60	209	37	1.1	0.4	204	56	1.6	0.2	1.1	0.3	178	44	N
Metoprolol	275	31	333	4	1.2	0.1	275	25	1.2	0.1	1.0	0.0	271	42	N
Propranolol	177	20	224	9	1.3	0.2	200	44	1.5	0.2	1.0	0.3	204	47	N
Cyclosporine A	39	1	77	7	2.0	0.2	60	29	2.4	0.2	1.9	0.3	59	28	N^{^a}
Ritonavir	22	1	102	10	4.6	0.5	72	61	7.9	1.1	4.6	0.9	73	53	N^{^a}
Erythromycin	8	2	68	3	8.0	1.5	36	30	7.6	0.2	10.8	0.3	41	37	N^{^a}
Sunitinib	72	8	197	9	2.7	0.3	92	7	1.1	^{^b}	1.2	^{^b}	100	17	Y
Simvastatin	22	3	86	7	4.0	0.7	52	11	1.2	0.4	0.8	0.1	45	4	Y
Gefitinib	53	8	237	31	4.5	0.9	106	33	1.6	0.4	1.5	0.1	108	31	Y
Zidovudine	13	2	59	7	4.5	0.7	42	19	0.7	^{^b}	0.8	0.2	56	26	Y
Prazosin	73	14	332	10	4.5	0.9	136	19	1.3	0.1	0.9	0.3	149	21	Y
Imatinib	76	10	371	37	4.9	0.8	170	90	1.2	0.9	1.5	^{^b}	229	81	Y
MK571	22	1	105	7	4.9	0.4	51	12	0.7	0.2	0.6	0.1	63	4	Y
Coumestrol	<23	1	117	9	>5.1	0.4	31	7	1.4	0.2	1.3	0.2	27	6	Y
SN38^{^e}	13	1	72	2	5.7	0.6	36	6	0.8	0.1	1.1	0.2	34	6	Y
Daunorubicin	22	7	128	18	5.8	2.0	79	59	4.8	1.1	2.3	^{^b}	80	50	Y^{^c}
Cimetidine	6	2	35	7	6.1	2.7	8	2	1.0	0.3	1.2	0.2	15	3	Y
Topotecan HCl ^{^d}	<9	1	61	13	>6.4	1.4	13	2	1.1	0.3	1.4	^{^b}	18	7	Y
Genistein	39	^{^b}	265	33	6.9	^{^b}	69	22	1.7	0.5	1.1	0.5	62	10	Y
Mitoxantrone	27	^{^b}	197	56	7.3	^{^b}	56	67	0.5	0.7	1.3	0.5	37	7	Y
Rifampicin	31	11	68	10	7.3	2.9	67	59	7.9	1.5	2.2	0.9	50	27	Y^{^c}
Daidzein	22	1	311	36	14.1	1.6	84	15	0.9	0.2	1.8	0.7	63	17	Y
Pitavastatin	5	1	70	8	15.3	1.8	18	4	0.7	0.1	0.7	0.2	34	6	Y
PhIP	32	7	509	12	15.8	3.5	234	16	1.2	0.3	1.0	0.2	252	12	Y
Irinotecan	4	1	65	4	16.9	3.6	23	15	3.5	1.4	2.0	0.4	21	9	Y
Fluvastatin	<2	1	99	10	>43	4.1	26	5	0.7	0.1	1.1	0.3	35	10	Y

ERi, efflux ratio in the presence of inhibitor; N, not substrate (no); P_app (in nm/s), apparent permeability either from apical to basolateral (AB) or from basolateral to apical (BA); P_appi (in nm/s), apparent permeability in the presence of inhibitor; Y, substrate (yes).
↵^a ER in M-BCRP ≥2 but equivalent in MDCKII and insensitive to Ko143 (1 µM).
↵^b No S.D. [one or two triplicate(s) were discarded due to high lucifer yellow values or disproportionate recovery].
↵^c ER in M-BCRP ≥2 significantly different in MDCKII, but insensitive to Ko143 (1 µM).
↵^d Tested at 0.5 µM (toxic at 1 µM).
↵^e SN38 (7-Ethyl-10-hydroxycamptothecin); active metabolite of irinotecan.