Drug Metabolism in Drug Design and Development Basic Concepts and Practice

Cisplatin is a substrate for

MRP2 but not for MRP1.Folic acid and monovalentbile salts such as cholate,taurocholate, andglycocholateare substrates for MRP3but not for MRP1and MRP2.

ABCC2

MRP2,

CMOAT

Intestine, liver,

kidney, brain,placenta, cancer cells

Probenecid, indomethacin,

MK571, cyclosporine(dexamethasone,St. John’s wort)

Intrinsic ATPase

activity andATP hydrolysis

ABCC3

MRP3

Intestine, pancreas,

placenta, adrenalcortex, liver, kidney,prostate, cancer cells

Benzbromarone

(phenobarbital)

Intrinsic ATPase

activity andATP hydrolysis

ABCC4

MRP4

Prostate, lung, adrenals,

ovary, testis, pancreas,small intestine,cancer cells

Nucleoside analogues and

cyclic nucleotides(cGMP and cAMP)

Probenecid, slidenafil

Intrinsic ATPase

activity andATP hydrolysis

Unlike MRP4, MRP5

transport GS conjugatesbut not E17

bG.

MRP4: adefovir, zidovudine,

monophospate

MRP5: adefovir,

mercaptopurine

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