SUBTYPE:Transporter Assays
APPLICATION & SPECIALITY USES:ADME-Toxicology Products and Services

Transporters as Therapeutic, Toxicity, and Delivery Targets

Our OPTI-TARGET Panel consists of validated and novel transporter targets implicated in diseases, toxicity, and tissue targeting. Transporters available in this panel can aid in the discovery of new classes of transporter-targeted therapeutics. We provide customized OPTI-TARGET Panel research services for rapid compound screening and comprehensive transporter profiling.

Aberrant transporter activity is associated with a variety of diseases, including cancer, neurological disorders, and diabetes. Consequently, the rational design of transporter-targeting molecules represents an enormous opportunity for developing new therapeutic and diagnostic agents with novel mechanisms of action, and improved efficacy and safety.

Transporters as Therapeutic Targets

Many transporters are important modulators of the movement and homeostasis of signaling molecules and nutrients. As a result, transporter proteins themselves represent attractive targets in the treatment of various diseases. Therapeutic intervention, through the inhibition or enhancement of transporter activities, has produced numerous drugs. For instance, many drugs for mental and neurological disorders including depression, schizophrenia, and epilepsy, function by targeting neurotransmitter reuptake transporters. Likewise, many other drugs work by targeting key transporters involved in diabetes, cystic fibrosis, high cholesterol, and gout. Several novel transporter-based approaches are also currently under investigation. Examples include using transporter inhibitors to block tumor growth, control cellular oxidative stress, treat schizophrenia, and reduce bile acid reabsorption.

Transporters as Toxicity Targets

Unintended, off-target interactions of drugs with transporters involved in key physiological processes can lead to serious adverse effects. In such cases, toxicity is often caused by the undesired accumulation of the drug in organs such as the kidneys and liver. For example, certain platinum-based drugs induce severe nephrotoxicity as a result of unwanted platinum accumulation in the kidney. The drug appears to accumulate due to uptake by OCT2; therefore, the toxicity could potentially be prevented by co-dosing patients with OCT2 inhibitors. Using similar strategies, it should be possible to decrease the toxicity of numerous marketed drugs that currently exhibit unwanted accumulation in various tissues and organs, including heart, liver, and brain.

Transporters as Delivery Targets

Because many transporters are tissue-specific, tissue-enriched, or dysregulated in diseases, transporters can be used to achieve efficient, targeted delivery of drugs and imaging agents. Transporter-targeting approaches can be particularly attractive for intracellular drug-delivery or prodrug designs, as they circumvent receptor-mediated endocytosis. One example comes from the class of nucleoside analog drugs (e.g. gemcitabine, 5-FU, zidovudine). These drugs rely on the nucleoside transporters (CNTs and ENTs) for efficient cellular uptake. Thus, levels of these transporters are an important determinant of treatment efficacy. Transporters are also important targets for diagnostic imaging. The most successful PET imaging probe, 18F-FDG, is transported by GLUT1, a glucose transporter up-regulated in many cancers; several other cancer imaging probes also target transporters that are enriched in tumors (e.g. NET/123I-MIBG, LAT1/18F-FET, xCT/BAY-94-9392). In addition to tumor imaging, several transporter-targeting probes are under development for detecting various neurological disorders, diabetes, and cardiovascular diseases. Similar to the GPCR targets that changed the pharmaceutical industry 25 years ago, membrane transporters represent enormous potential as therapeutic and diagnostic targets for various diseases

TransporterPhysiological roleGeneMajor tissue distributionRelated disease/ADRExamples of interacting xenobioticsAvailable Species
ASBTBile acid uptakeSLC10A2Ileum, kidney, biliary tract (apical)Cholestatic liver diseases, NASH, primary bile acid malabsorption,
constipation, and
asc-1Amino acid transportSLC7A10Brain, heart, placenta, skeletal muscle and kidneyLearning and memory impairment, schizophreniaBMS-466442Human
ASCT2Amino acid transportSLC1A5Lung, skeletal muscle, large intestine, kidney, testis, adipose tissue, tumor cellsCancerGPNA,
BSEPBile acid effluxABCB11LiverPFIC II, drug induced cholestasis and hepatitisTroglitazone, rifampicin, benzbromarone, bosentan,
cyclosporine A
Human, rat, dog
CNT1Nucleoside uptakeSLC28A1Liver, kidney, small intestine, tumor cellsCancer, infectious diseasesGemcitabine, cytarabine, azacitidine, zalcitabine, floxuridineHuman, rat
CNT2Nucleoside uptakeSLC28A2Kidney (apical membrane), liver, heart, brain, placenta, pancreas, skeletal muscle, colon, rectum, small intestine, lymphocytes, tumor cellsCancer, infectious diseasesRibavirin,
cladribine, didanosine, fludarabine, clofarabine, floxuridine, acacitidine
Human, rat
CNT3Nucleoside uptakeSLC28A3Pancreas, trachea, bone marrow, and mammary gland, intestine, brain, heart, prostrate, liver, tumor cellsCancer, infectious diseasesGemcitabine, azacitidine, mercaptopurine, fludarabine, clofarabine, cladribine, floxuridineHuman, rat
DATNeurotransmissionSLC6A3Brain (dopaminergic neurons), gutParkinson disease, Tourette syndrome, ADHD, addiction, major affective disoordersAltropane, vanoexerine, difluoropine, iometopane, DBL-583, GBR-12783, RTI-229,
EAAT1NeurotransmissionSLC1A3Brain (astrocytes, Bergmann glia), heart, skeletal muscle, placentaAlzheimer's disease, Huntington's disease, epilepsy, cerebellar ataxia type 7, schizophrenia, excitotoxicityRiluzole,
EAAT2NeurotransmissionSLC1A2Brain (astrocytes, Bergmann glia, neurons), liver, pancreasAmyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, epilepsy, ischemia, schizophrenia, excitotoxicityDihydrokainic acid, SYM-2081, WAY-213613, l-trans-PDCHuman
ENT1Nucleoside transportSCL29A1Heart, brain, mammary gland, erythrocytes and placenta, tumor cellsCancer, infectious diseasesGemcitabine,
zalcitabine, cytarabine, fludarabine, cladribine, azacitidine, pentostatin, decitabine
ENT2Nucleoside transportSLC29A2Skeletal muscle, liver, lung, placenta, brain, heart, kidney, ovarian tissues Cancer, infectious diseasesZidovudine, zalcitabine, cytarabine, fludarabine,
azacitidine, pentostatin, decitabine, cladribine
Human, rat
ENT4Nucleoside transport and extrasynaptic reuptakeSLC29A4Heart, brain, skeletal muscleDepression, schizophrenia, bipolar disorderTrazodone, decynium-22Human
GAT1NeurotransmissionSLC6A1Central and peripheral neurons (GABAergic neurons)Epilepsy, schizophrenia, ADHDTiagabine,
nipecotic acid,
deramciclane, hyperforin,
riluzole, SKF-89976A, NNC-711, SNAP-5114,
GAT2NeurotransmissionSLC6A13Brain (meninges, ependyma, choroid plexus), retina, liver, kidneyEpilepsyTiagabine,
nipecotic acid, riluzole, NNC05-2090,
SKF 89976A
GAT3NeurotransmissionSLC6A11Brain (GABAergic neurons)EpilepsyTiagabine,
nipecotic acid, riluzole,
SKF 89976A
GLYT1NeurotransmissionSLC6A9Brain, retina, liver, spleen, kidney, pancreas, uterus, stomach, lung, placenta, intestine SchizophreniaBitopertin, PF-04958242Human
NETNeurotransmissionSLC6A2Brain (non adrenergic neuronal somata, axons, dendrites), peripheral nervous system, adrenal gland (chromaffin cells), placentaDepression, orthostatic intolerance, anorexia nervosa, cardiovascular disorders, ADHDAtomoxetine, reboxetine, desipramine,
edivoxetine, viloxazine, maprotiline, nisoxetine,
OATP1B1Hepatic uptake of bilirubin and a variety of anionic drugsSLCO1B1Liver (hepatocytes)Statin-induced myopathy, hyperbilirubinemia, rotor syndromeCyclosporine A, rifampicin, gemfibrozil, ritonavir/lopinavirHuman
OATP1B3Hepatic uptake of bilirubin and a variety of anionic drugsSLCO1B3Liver (hepatocytes)Unconjugated hyperbilirubinemia, Rotor syndromeCyclosporine A, rifampicin, ritonavir/lopinavirHuman
OCT2Cation uptakeSLC22A2Kidney, small intestine, lung, placenta, thymus, brain (neurons, blood-brain barrier), inner earCytotoxicity of cisplatin, oxaliplatin and picoplatinCisplatin,
Human, rat
OCT3Cation uptake; extrasynaptic reuptakeSLC22A3Heart, skeletal muscle, brain (neurons, glial cells, plexus choroideus), small intestine, liver, lung, kidney, urinary bladder, mammary gland, skin blood vesselsProstate cancer, coronary heart disease, obsessive compulsive disorder, depressionOxaliplatin,
picoplatin, tetrabenazine, trazodone
Human, rat
OCTN1Ergothioneine uptakeSLC22A4Kidney, intestine, spleen, heart, skeletal muscle, brain, mammary gland, thymus, prostate, airways, testis, eye, fetal liver, sperm, immune cellsRheumatoid arthritis, Crohn's diseaseVerapamil,
quinidine, propafenone,
OCTN2Carnitine uptakeSLC22A5Skeletal muscle, kidney, prostate, lung, pancreas, heart, small intestine, adrenal gland, thyroid gland, liver, etc.Primary systemic carnitine deficiency, Crohn's diseaseVerapamil,
valproate, cephaloridine, pyrilamine
PCFTVitamin transportSLC46A1Small intestine, choroid plexus, kidney (proximal tubule), liver (sinusoidal), placentaHereditary folate malabsorption, cancerMethotrxate,
PEPT1Peptide uptakeSLC15A1Small intestine, kidney, pancreas, bile duct, liverInflammatory bowel diseaseGlycylsarcosine, bestatin, y-ALA, cephalexin, valacyclovir, cyclacillin,
PEPT2Peptide uptakeSLC15A2Apical surface of epithelial cells from kidney and choroid plexus; neurons, astrocytes (neonates), lung, mammary gland, spleen, enteric nervous systemLead exposureCefaclor, glycylsarcosine, bestatin,
RFCVitamin transportSLC19A1UbiquitousCancerMethotrxate, pemetrexed, tomudex,
SERTNeurotransmissionSCL6A4Brain, peripheral nervous system, placenta, epithelium cells, plateletsAnxiety, depression, autism gastrointestinal disorders, premature ejaculation, obesity, schizophrenia, OCDSertraline, fluvoxamine, fluoxetine, citalopram, zimelidine, dapoxetine, paroxetine, escitalopram,
SGLT2Glucose transportSLC5A2Kidney, brain, liver, heart muscle, thyroid, salivary glandsType II Diabetes, familial renal glucosuriaCanagliflozin, dapagliflozin, empagliflozin, tofogliflozin, ipragliflizin, remogliflozin, sotagliflozin, ertugliflozinHuman
SNAT1Amino acid transportSLC38A1Brain, retina, heart, placenta, adrenal glandSuicidal behavior, cancerMeAIBHuman
SNAT2Amino acid transportSLC38A2UbiquitousSchizophrenia, cancerMeAIBHuman
THTR1Vitamin transportSLC19A2UbiquitousThiamine-responsive megaloblastic anemia syndromeFedratinib, amprolium, pyrithiamine, oxythiamineHuman
THTR2Vitamin transportSLC19A3UbiquitousBiotin-responsive basal ganglia disease, Wernicke's encephalopathyFedratinib, amprolium, pyrithiamine, oxythiamineHuman
URAT1Uric acid renal tubular reabsorptionSLC22A12KidneyRenal hypo-uricemia, goutLesinurad,
KUX-1151, benzbromarone
xCTAmino acid transport and neurotransmissionSLC7A11Macrophages, brain, retinal pigment cells, liver, kidney, tumor cellsCancer, epilepsy, neurodegenerative diseasesSulfasalazine,