Substrates And Inhibitors

Substrates and inhibitors of transporters are, in general, less selective than substrates and inhibitors of P450 enzymes. Tables 4.3 and 4.4 summarize known substrates and inhibitors of select ABC and SLC transporters.

Table 4.3. Select ABC transporter substrates and inhibitors Transporter

(alias)

Gene

Substrates

Inhibitors

MDR1

ABCB1

Digoxin, loperamide,

Cyclosporine,

(P-gp,

berberine, irinotecan,

quinidine,

ABCB1)

doxorubicin,

tariquidar,

vinblastine, paclitaxel,

verapamil

fexofenadine

MDR3

ABCB4

Phosphatidylcholine,

Verapamil,

(ABCB4)

paclitaxel, digoxin,

cyclosporine

vinblastine

BCRP

ABCG2

Mitoxantrone,

Oestrone, 17ß-

(MXR)

methotrexate,

oestradiol,

topotecan, imatinib,

fumitremorgin C

irinotecan, statins,

sulfate conjugates,

porphyrins

MRP2

ABCC2

Glutathione and

Cyclosporine,

(ABCC2,

glucuronide conjugates,

delaviridine,

cMOAT)

methotrexate, etoposide,

efavirenz,

mitoxantrone, valsartan,

emtricitabine

olmesartan,

glucuronidated SN-38

MRP3

ABCC3

Oestradiol-17ß-

Delaviridine,

(ABCC3)

glucuronide,

efavirenz,

methotrexate,

emtricitabine

fexofenadine,

glucuronate conjugates

MRP4

ABCC4

Adefovir, tenofovir, cyclic

Celecoxib,

(ABCC4)

AMP,

diclofenac

dehydroepiandrosterone

sulfate, methotrexate,

topotecan, furosemide,

cyclic GMP, bile acids

plus glutathione

BSEP

ABCB11

Taurocholic acid,

Cyclosporin A,

(SPGP,

pravastatin, bile acids

rifampicin,

cBAT,

glibenclamide

ABCB11)

Table 4.4. Select SLC transporter substrates and inhibitors

Transporter

(alias)

Gene

Substrates

Inhibitors

OATP1A2

SLCO1A2

Oestrone-3-sulfate,

Naringin,

(OATP-A)

dehydroepiandrosterone sulfate, fexofenadine, bile salts, methotrexate, bromosulphophthalein, ouabain, digoxin, levofloxacin, statins

ritonavir, lopinavir, saquinavir, rifampicin

OATP1B1

SLCO1B1

Bromosulphophthalein,

Saquinavir,

(OATP-C,

oestrone-3-sulfate,

ritonavir,

OATP2,

oestradiol-17b-

lopinavir,

LST-1)

glucuronide, statins, repaglinide, valsartan, olmesartan, bilirubin glucuronide, bilirubin, bile acids

rifampicin, cyclosporine

OATP1B3

SLCO1B3

Bromosulphophthalein,

Rifampicin,

(OATP-8)

cholecystokinin 8, statins, digoxin, fexofenadine, telmisartan glucuronide, telmisartan, valsartan, olmesartan, oestradiol-17-b-glucuronide, bile acids

cyclosporine, ritonavir, lopinavir

OATP2B1

SLCO2B1

Oestrone-3-sulfate,

Rifampicin,

(OATP-B)

bromosulphophthalein, taurocholate, statins, fexofenadine, glyburide, taurocholate

cyclosporine

OAT1

SLC22A6

Para-aminohippurate, adefovir, cidofovir, zidovudine, lamivudine, zalcitabine, acyclovir, tenofovir, ciprofloxacin, methotrexate

Probenecid, novobiocin

OAT3

SLC22A8

Oestrone-3-sulfate, nonsteroidal anti-inflammatory drugs, cefaclor, ceftizoxime, furosemide, bumetanide

Probenecid, novobiocin

OCT1

SLC22A1

Tetraethylammonium, N-methylpyridinium, metformin, oxaliplatin

Quinine, quinidine, disopyramide

OCT2

SLC22A2

Continued

Table 4.4 Continued

Transporter

(alias)

Gene

Substrates

Inhibitors

N-Methylpyridinium,

Cimetidine,

tetraethylammonium,

pilsicainide,

metformin, pindolol,

cetirizine,

procainamide, ranitidine

testosterone,

amantadine, amiloride,

quinidine

oxaliplatin, varenicline

PEPT1

SLC15A1

Glycylsarcosine, cephalexin, cefadroxil, bestatin, valacyclovir, enalapril, aminolevulinic acid, captopril, dipeptides, tripeptides

Glycyl-proline

PEPT2

SLC15A2

Glycylsarcosine, cephalexin, cefadroxil, bestatin, valacyclovir, enalapril, aminolevulinic acid, captopril, dipeptides, tripeptides

Zofenopril, fosinopril

MATE1

SLC47A1

Metformin, N-methylpyridinium, tetraethylammonium

Quinidine, cimetidine, procainamide

MATE2-K

SLC47A2

Metformin, N-methylpyridinium, tetraethylammonium

Cimetidine, quinidine, pramipexole

Data from The International Transporter Consortium (2010)

Data from The International Transporter Consortium (2010)

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