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Bioivt Transporter Catalog DG V3

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Transporter Assay Catalog Single Transporter Models Single Transporter Models Subcellular Transporter Relevance Gene Transporter Assay Species2 Cell Model3 Probe Substrate Inhibition 1 Localization in Type Type Assay Model Positive Control ASBT Bile acid uptake SLC10A2 Uptake IA H Apical MDCK-II Taurocholate NaCDC asc-1 Amino acid transport SLC7A10 Uptake IA H Basolateral MDCK-II Glycine Serine ASCT2 Amino acid transport SLC1A5 Uptake IA H Apical MDCK-II Glutamine Alanine ATB0+ Amino acid transport SLC6A14 Uptake IA H Apical MDCK-II Leucine N-Ethylmaleimide BAT1, CSNU3 Amino acid transport SLC7A9 Uptake IA H Apical MDCK-II Proline BCRP FDA & EMA DDI guidances; intestinal and BBB efflux, ABCG2 Efflux BD H Apical Caco-2 clone3 Genistein Chrysin biliary secretion, renal tubular secretion and drug resistance VA H, R N/A Vesicle CCK-8 Bromosulfophthalein BD H Apical MDCK-II Prazosin KO143 BSEP EMA DDI guidance; biliary secretion of bile salts, drug ABCB11 Efflux VA H, R, D N/A Vesicle Taurocholate Rifampicin induced liver injury CAT1 Amino acid transport SLC7A1 Uptake IA H Basolateral MDCK-II Arginine Lysine CAT2B Amino acid transport SLC7A2 Uptake IA H Basolateral MDCK-II Arginine CAT3 Amino acid transport SLC7A3 Uptake IA H Basolateral MDCK-II Arginine Lysine CHT Choline transport SLC5A7 Uptake IA H Basolateral MDCK-II Choline CNT1 Nucleoside uptake SLC28A1 Uptake IA H, R Apical MDCK-II Uridine Adenosine CNT2 Nucleoside uptake SLC28A2 Uptake IA H, R Apical MDCK-II Uridine Adenosine CNT3 Nucleoside uptake SLC28A3 Uptake IA H, R Apical MDCK-II Uridine Adenosine 3-Guanidinopropionic CRT Creatine transport SLC6A8 Uptake IA H Basolateral MDCK-II Creatine acid DAT Neurotransmission; validated therapeutic target SLC6A3 Uptake IA H Apical MDCK-II Dopamine Venlafaxine EAAT1 Neurotransmission SLC1A3 Uptake IA H Basolateral MDCK-II Glutamic acid Cysteic acid EAAT2 Neurotransmission SLC1A2 Uptake IA H Basolateral MDCK-II Glutamic acid Cysteic acid EAAT3 Neurotransmission SLC1A1 Uptake IA H Apical MDCK-II Glutamic acid Way-213613 ENT1 Nucleoside transport SCL29A1 Uptake IA H Apical (and MDCK-II Adenosine NBMPR Basolateral) ENT2 Nucleoside transport SLC29A2 Uptake IA H, R Basolateral MDCK-II Hypoxanthine Adenosine ENT4 / PMAT Nucleoside transport and extrasynaptic reuptake SLC29A4 Uptake IA H Basolateral MDCK-II Metformin or MPP+ Decynium-22 GAT1 Neurotransmission; validated therapeutic target SLC6A1 Uptake IA H Apical MDCK-II GABA Nipecotic acid GAT2 Neurotransmission SLC6A13 Uptake IA H Basolateral MDCK-II GABA Nipecotic acid GAT3 Neurotransmission SLC6A11 Uptake IA H Apical MDCK-II GABA Nipecotic acid GLYT1 Neurotransmission SLC6A9 Uptake IA H Basolateral MDCK-II Glycine Sarcosine GLYT2 Neurotransmission SLC6A5 Uptake IA H Basolateral MDCK-II Glycine Org25543 LAT1 Amino acid transport SLC7A5 Uptake IA H Basolateral MDCK-II Leucine JPH203 MATE1 Biliary secretion and renal tubular secretion SLC47A1 Efflux IA H, R Apical MDCK-II Metformin Cimetidine MATE2-K Renal tubular secretion SLC47A2 Efflux IA H Apical MDCK-II Metformin Cimetidine MCT1 Lactate and ketone body transport SLC16A1 Uptake IA H Apical MDCK-II 2-Thiophene-glyoxylic acid Phloretin MRP1 Drug resistance ABCC1 Efflux VA H N/A Vesicle Estradiol-17-ß-D-glucuronide Benzbromarone MRP2 Biliary secretion, renal tubular secretion, drug resistance ABCC2 Efflux VA H, M, R, D N/A Vesicle Estradiol-17-ß-D-glucuronide Benzbromarone Bile acid transport, bilirubin glucuronide transport MRP3 ABCC3 Efflux VA H N/A Vesicle Estradiol-17-ß-D-glucuronide Benzbromarone MRP4 Renal tubular secretion; hepatic efflux; ABCC4 Efflux VA H N/A Vesicle Estradiol-17-ß-D-glucuronide Benzbromarone drug resistance NET Neurotransmission; validated therapeutic target SLC6A2 Uptake IA H Basolateral MDCK-II Dopamine Desipramine NTCP Hepatic bile salt uptake SLC10A1 Uptake IA H Basolateral MDCK-II Taurocholate NaCDC OAT1 FDA & EMA guidances; renal uptake SLC22A6 Uptake IA H Basolateral MDCK-II p-Aminohippurate Probenecid OAT2 Hepatic uptake; renal uptake SLC22A7 Uptake IA H Basolateral MDCK-II cGMP Indomethacin Estrone-3-sulfate or OAT3 FDA & EMA guidances; renal uptake SLC22A8 Uptake IA H, M Basolateral MDCK-II p-Aminohippurate Probenecid OAT4 Renal tubular reabsorption SLC22A11 Uptake IA H Apical MDCK-II Estrone-3-sulfate Indomethacin OATP1A2 Intestinal absorption; BBB penetration SLCO1A2 Uptake IA H Apical MDCK-II Estrone-3-sulfate Bromosulfophthalein OATP1B1 FDA & EMA DDI guidances; hepatic uptake SLCO1B1 Uptake IA H Basolateral MDCK-II, CHO3 Estradiol-17-ß-D-glucuronide Rifampicin OATP1B3 FDA & EMA DDI guidances; hepatic uptake SLCO1B3 Uptake IA H Basolateral MDCK-II, CHO3 Cholecystokinin-8 (CCK-8) Rifampicin OATP2B1 Hepatic uptake; intestinal uptake SLCO2B1 Uptake IA H N/A CHO3 Estrone-3-sulfate Bromosulfophthalein OCT1 EMA guidance; hepatic uptake SLC22A1 Uptake IA H, R Basolateral MDCK-II Metformin or MPP+ Quinidine OCT2BioIFDVA T& EM.cA guidances;om renal uptake SLC22A2 Uptake IA H, M, R, C Basolateral MDCK-II Metformin Quinidine OCT3 Renal uptake; extrasynaptic reuptake SLC22A3 Uptake IA H, R Basolateral MDCK-II Metformin or MPP+ Quinidine NET Neurotransmission; validated therapeutic target SLC6A2 Uptake IA H Basolateral MDCK-II Dopamine Desipramine NTCP Hepatic bile salt uptake SLC10A1 Uptake IA H Basolateral MDCK-II Taurocholate NaCDC OAT1 FDA & EMA guidances; renal uptake SLC22A6 Uptake IA H Basolateral MDCK-II p-Aminohippurate Probenecid OAT2 Hepatic uptake; renal uptake SLC22A7 Uptake IA H Basolateral MDCK-II cGMP Indomethacin Single Transporter Models OAT3 FDA & EMA guidances; renal uptake SLC22A8 Uptake IA H, M SubcellularBasolateral MDCK-II Estrone-3-sulfate or Probenecid Transporter Relevance Gene Transporter Assay Species2 Cell Model3 Probep-Aminohippurate Substrate Inhibition 1 Localization in OAT4 Renal tubular reabsorption SLC22A11 TUptakeype TIAype H AssayApical Model MDCK-II Estrone-3-sulfate PositiveIndomethacin Control ASBTOATP1A2 BileIntestinal acid uptakeabsorption; BBB penetration SLC10A2SLCO1A2 Uptake IA H Apical MDCK-II TEstrone-3-sulfateaurocholate NaCDCBromosulfophthalein asc-1OATP1B1 AminoFDA & acidEMA transport DDI guidances; hepatic uptake SLC7A10SLCO1B1 Uptake IA H Basolateral MDCK-IIMDCK-II, CHO 3 GlycineEstradiol-17-ß-D-glucuronide SerineRifampicin ASCT2OATP1B3 AminoFDA & acidEMA transport DDI guidances; hepatic uptake SLC1A5SLCO1B3 Uptake IA H ApicalBasolateral MDCK-IIMDCK-II, CHO 3 GlutamineCholecystokinin-8 (CCK-8) AlanineRifampicin AOTB0+ATP2B1 AminoHepatic acid uptake; transport intestinal uptake SLC6A14SLCO2B1 Uptake IA H ApicalN/A MDCK-IICHO3 LeucineEstrone-3-sulfate N-EthylmaleimideBromosulfophthalein BOCT1AT1, CSNU3 AminoEMA guidance; acid transport hepatic uptake SLC7A9SLC22A1 Uptake IA HH, R ApicalBasolateral MDCK-II ProlineMetformin or MPP+ Quinidine BCRPOCT2 FDA & EMA DDIguidances; guidances; renal intestinal uptake and BBB efflux, ABCG2SLC22A2 EUptakefflux BDIA HH, M, R, C ApicalBasolateral Caco-2MDCK-II clone3 GenisteinMetformin ChrysinQuinidine biliary secretion, renal tubular secretion and drug OCT3 resistanceRenal uptake; extrasynaptic reuptake SLC22A3 Uptake IA H, R Basolateral MDCK-II Metformin or MPP+ Quinidine OCTN1 Renal tubular reabsorption SLC22A4 Uptake VIAA H,H R N/AApical VMDCK-IIesicle CCK-8Ergothioneine BromosulfophthaleinVerapamil OCTN2 Renal tubular reabsorption, critical genetic polymorphism SLC22A5 Uptake BDIA H Apical MDCK-II PrazosinCarnitine KO143Verapamil SLC51A1 & BSEPOST -OST EMBileA acid DDI transport guidance; biliary secretion of bile salts, drug ABCBSLC 51A211 EUptakefflux VIAA H,H R, D N/ABasolateral VMDCK-IIesicle TTCAaurocholate Rifampicin induced liver injury CPAAT2T1 Amino acid transport SLC7A1SLC36A2 Uptake IA H BasolateralApical MDCK-II ArginineGlycine Lysine CPCFTAT2B AminoVitamin acid transport transport SLC7A2SLC46A1 Uptake IA H BasolateralApical MDCK-II ArginineMethotrexate Bromosulfophthalein CPEPT1AT3 AminoIntestinal acid uptake, transport prodrug strategy SLC7A3SLC15A1 Uptake IA H BasolateralApical MDCK-II ArginineGly-Sar LLosartanysine CHTPEPT2 CholineRenal tubular transport reabsorption SLC5A7SLC15A2 Uptake IA H BasolateralApical MDCK-II CholineGly-Sar Losartan FDA & EMA DDI guidances; intestinal and BBB efflux, ABCB1 BD, VA in MDCK-II, CNT1P-gp Nucleosidebiliary secretion, uptake renal tubular secretion, drug resistance SLC28A1(MDR1) UptakeEfflux IAvesicles H, R Apical (in cells) MDCK-IICaco-2, vesicles UridineDigoxin, quinidine AdenosineVerapamil, elacridar CNT2PROT NucleosideAmino acid uptaketransport SLC28A2SLC6A7 Uptake IA H,H R ApicalBasolateral MDCK-II UridineProline Adenosine CNT3RFC NucleosideFolate transport uptake SLC28A3SLC19A1 Uptake IA H,H R ApicalBasolateral MDCK-II UridineMethotrexate AdenosineBromosulfophthalein 3-Guanidinopropionic CRTSERT CreatineNeurotransmission; transport validated therapeutic target SLC6A8SCL6A4 Uptake IA H Basolateral MDCK-II CreatineSerotonin acidFluoxetine Glucose and galactose transport; validated therapeutic DSGATLT1 Neurotransmission;target validated therapeutic target SLC6A3SLC5A1 Uptake IA H Apical MDCK-II DopamineMethyl- -D-glucopyranoside VPhlorizinenlafaxine EASGALT2T1 NeurotransmissionGlucose transport; validated therapeutic target SLC1A3SLC5A2 Uptake IA H BasolateralApical MDCK-II GlutamicMethyl- -D-glucopyranoside acid CysteicPhlorizin acid Pantothenate (vitamin EASMVTAT2 NeurotransmissionVitamin transport SLC1A2SLC5A6 Uptake IA H BasolateralApical MDCK-II GlutamicBiotin (vitamin acid B7) CysteicB5) acid EASNAT3T1 NeurotransmissionAmino acid transport SLC1A1SLC38A1
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  • Analysis of Dynamic Molecular Networks for Pancreatic Ductal

    Analysis of Dynamic Molecular Networks for Pancreatic Ductal

    Pan et al. Cancer Cell Int (2018) 18:214 https://doi.org/10.1186/s12935-018-0718-5 Cancer Cell International PRIMARY RESEARCH Open Access Analysis of dynamic molecular networks for pancreatic ductal adenocarcinoma progression Zongfu Pan1†, Lu Li2†, Qilu Fang1, Yiwen Zhang1, Xiaoping Hu1, Yangyang Qian3 and Ping Huang1* Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors. The rapid progression of PDAC results in an advanced stage of patients when diagnosed. However, the dynamic molecular mechanism underlying PDAC progression remains far from clear. Methods: The microarray GSE62165 containing PDAC staging samples was obtained from Gene Expression Omnibus and the diferentially expressed genes (DEGs) between normal tissue and PDAC of diferent stages were profled using R software, respectively. The software program Short Time-series Expression Miner was applied to cluster, compare, and visualize gene expression diferences between PDAC stages. Then, function annotation and pathway enrichment of DEGs were conducted by Database for Annotation Visualization and Integrated Discovery. Further, the Cytoscape plugin DyNetViewer was applied to construct the dynamic protein–protein interaction networks and to analyze dif- ferent topological variation of nodes and clusters over time. The phosphosite markers of stage-specifc protein kinases were predicted by PhosphoSitePlus database. Moreover, survival analysis of candidate genes and pathways was per- formed by Kaplan–Meier plotter. Finally, candidate genes were validated by immunohistochemistry in PDAC tissues. Results: Compared with normal tissues, the total DEGs number for each PDAC stage were 994 (stage I), 967 (stage IIa), 965 (stage IIb), 1027 (stage III), 925 (stage IV), respectively. The stage-course gene expression analysis showed that 30 distinct expressional models were clustered.
  • Analysis of OAT, OCT, OCTN, and Other Family Members Reveals 8

    Analysis of OAT, OCT, OCTN, and Other Family Members Reveals 8

    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.23.887299; this version posted December 26, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Reclassification of SLC22 Transporters: Analysis of OAT, OCT, OCTN, and other Family Members Reveals 8 Functional Subgroups Darcy Engelhart1, Jeffry C. Granados2, Da Shi3, Milton Saier Jr.4, Michael Baker6, Ruben Abagyan3, Sanjay K. Nigam5,6 1Department of Biology, University of California San Diego, La Jolla 92093 2Department of Bioengineering, University of California San Diego, La Jolla 92093 3School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla 92093 4Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, San Diego, CA, USA 5Department of Pediatrics, University of California San Diego, La Jolla 92093 6Department of Medicine, University of California San Diego, La Jolla 92093 *To whom correspondence should be addressed: [email protected] Running title: Functional subgroups for SLC22 1 bioRxiv preprint doi: https://doi.org/10.1101/2019.12.23.887299; this version posted December 26, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Among transporters, the SLC22 family is emerging as a central hub of endogenous physiology.
  • Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level

    Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level

    International Journal of Molecular Sciences Review Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level Sweilem B. Al Rihani 1 , Lucy I. Darakjian 1, Malavika Deodhar 1 , Pamela Dow 1 , Jacques Turgeon 1,2 and Veronique Michaud 1,2,* 1 Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; [email protected] (S.B.A.R.); [email protected] (L.I.D.); [email protected] (M.D.); [email protected] (P.D.); [email protected] (J.T.) 2 Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada * Correspondence: [email protected]; Tel.: +1-856-938-8697 Abstract: The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies.