Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.1 (

Continued

)

Gene

Protein name Tissue distribution

Substrate properties

Selected inhibitor

and (inducer)

Driving force

ABCC5

MRP5

Ubiquitous (mainly in

skeletal muscle, heartand brain), cancer cells

Probenecid, slidenafil

Intrinsic ATPase

activity andATP hydrolysis

ABCG2

BCRP,

MXR,ABCP

Placenta, intestine, liver,

breast, brain, cancer cells

Broad substrate specificity,

partly overlapping betweenP-gp and MRP substrates.

Ko143, fumitremorgin,

HIV inhibitors,novobiocin, imitinib(Gleevac), gefitinib(Iressa)

Intrinsic ATPase

activity andATP hydrolysis

Substrates of BCRP can be

either hydrophobic orhydrophilic, negatively orpositively charged,xenobioticsor endobiotics, andunconjugated or conjugated,such as estrone sulfate,lysotracker, methotrexate,sulfasalazine, topotecanand imitinib

Solute Carrier TransportersSLC10A1

NTCP

Liver

Bile salts, such as taurocholate

All major bile salts,

BQ-123, CsA

Na

+

dependent

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