Affinage

ABCB1

ATP-dependent translocase ABCB1 · UniProt P08183

Round 2 corrected
Length
1280 aa
Mass
141.5 kDa
Annotated
2026-04-28
130 papers in source corpus 30 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCB1 (P-glycoprotein/MDR1) is an ATP-dependent efflux transporter that uses the energy of ATP hydrolysis to translocate a broad spectrum of hydrophobic substrates—including cytotoxic drugs, lipids, and amyloid-β peptides—from the cytoplasmic face of the membrane to the extracellular space, thereby conferring multidrug resistance and regulating substrate bioavailability across pharmacological barriers (PMID:2876781, PMID:3022150, PMID:2568355, PMID:8898203, PMID:16239972). Substrate polyspecificity arises from a large, flexible drug-binding pocket within the transmembrane domains containing multiple overlapping sites, while ATP-driven closure of the two nucleotide-binding domains into a sandwich dimer couples hydrolysis of two ATP molecules per transport cycle to conformational changes that power unidirectional efflux (PMID:14576852, PMID:17237262, PMID:25640267). At the blood–brain barrier, ABCB1 mediates both influx limitation and active efflux of substrates including Aβ peptides, and its loss increases cerebral amyloid deposition (PMID:16239972, PMID:26585058). ABCB1 expression is regulated transcriptionally by nuclear receptors (CAR), cytokines, STAT5a, and the HOTAIR/miR-145 axis, and post-translationally by USP7-mediated deubiquitination that controls protein stability (PMID:37408070, PMID:34336684, PMID:30698830, PMID:36291159).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1986 High

    Cloning and transfection of MDR1 established that a single gene encodes a 1280-aa membrane glycoprotein with two TMD–NBD cassettes sufficient to confer the complete multidrug-resistance phenotype, resolving whether MDR required one or multiple gene products.

    Evidence cDNA sequencing, homology analysis, and gain-of-function transfection into drug-sensitive cells

    PMID:2876781 PMID:3022150 PMID:3768958

    Open questions at the time
    • No atomic-resolution structure yet available
    • Substrate recognition mechanism unknown
    • Stoichiometry of ATP utilization not determined
  2. 1988 High

    Point mutations within ABCB1 that alter the drug cross-resistance profile demonstrated that substrate specificity is encoded within the P-glycoprotein sequence itself, not by accessory factors.

    Evidence Sequencing of spontaneous mdr1 mutants from colchicine-selected cells, site-directed mutagenesis, and drug resistance profiling

    PMID:2897240

    Open questions at the time
    • Exact residues forming the drug-binding pocket not mapped
    • No structural basis for how single mutations shift specificity
  3. 1989 High

    Reconstitution of ATP-dependent, unidirectional daunomycin transport in membrane vesicles proved that P-glycoprotein is a bona fide ATP-driven efflux pump, ruling out channel or facilitator models.

    Evidence Canalicular and brush-border membrane vesicle transport assays with non-hydrolyzable ATP analogue controls

    PMID:1347031 PMID:2568355

    Open questions at the time
    • Number of ATPs consumed per transport cycle not yet quantified
    • Lipid substrate transport not yet tested
  4. 1996 High

    Demonstration that ABCB1 translocates short-chain phospholipid and sphingolipid analogues to the outer leaflet expanded its function beyond drug efflux to a broad-specificity lipid flippase.

    Evidence Fluorescent lipid analogue translocation assays in stably transfected epithelial monolayers with energy-depletion and inhibitor controls

    PMID:8898203

    Open questions at the time
    • Physiological relevance of lipid flippase activity in non-epithelial tissues unclear
    • Structural basis of lipid vs drug recognition not resolved
  5. 2000 High

    The C3435T synonymous SNP and the 1236T-2677T-3435T haplotype were linked to altered intestinal P-gp expression and drug pharmacokinetics, establishing that common ABCB1 genetic variants have functional consequences in vivo.

    Evidence Genotype–phenotype correlation in human volunteers using Western blot, immunohistology, digoxin/fexofenadine pharmacokinetics, and in vitro efflux assays of expressed alleles

    PMID:10716719 PMID:11503014

    Open questions at the time
    • Causal SNP vs linkage disequilibrium not fully distinguished
    • Mechanism by which synonymous SNP alters expression/function unresolved
  6. 2003 High

    Synthesis of photoaffinity labeling, mutagenesis, and ATPase data established the two-ATP-per-substrate stoichiometry and located multiple overlapping drug-binding sites within the TMDs, providing a mechanistic framework for polyspecificity.

    Evidence Photoaffinity labeling with [125I]-IAAP, site-directed mutagenesis, ATPase measurements across multiple labs

    PMID:14576852

    Open questions at the time
    • No high-resolution drug-bound structure
    • Allosteric coupling between binding pocket and NBDs not structurally resolved
  7. 2005 High

    Genetic ablation and pharmacological inhibition of P-gp at the BBB showed that ABCB1 mediates Aβ peptide clearance from the CNS, linking the transporter to Alzheimer's disease amyloid pathology.

    Evidence Radiolabeled Aβ microinjection in Pgp-null vs WT mice, P-gp inhibitor studies in APP-transgenic mice, histological amyloid quantification

    PMID:16239972

    Open questions at the time
    • Whether ABCB1 transports Aβ directly or via an intermediary not fully resolved
    • Relevance to human AD progression not established
  8. 2006 High

    The 1236T-2677T-3435T haplotype was shown to alter P-gp conformation without changing expression levels, revealing that synonymous codon changes affect cotranslational folding and thereby substrate/inhibitor interaction profiles.

    Evidence Cell-based expression of WT vs polymorphic P-gp with drug interaction and conformational analysis

    PMID:17185560

    Open questions at the time
    • Direct structural evidence for altered folding not obtained
    • Generalizability of cotranslational folding mechanism to other ABC transporters unknown
  9. 2007 High

    NBD dimerization studies showed that the power stroke for transport occurs upon formation of the pre-hydrolysis transition state, clarifying that it is ATP-dependent NBD closure—not hydrolysis product release—that drives the conformational switch.

    Evidence Mutational analysis of NBDs, biochemical ATP hydrolysis assays, structural studies with isolated NBDs

    PMID:17237262

    Open questions at the time
    • Full-length structure in transition state not captured
    • Coupling pathway from NBDs to TMD drug-binding pocket not resolved at residue level
  10. 2015 High

    Crystal structures of mouse P-gp in multiple inward-facing conformations combined with mutagenesis defined the large, flexible drug-binding pocket and the structural basis of polyspecificity, while quantitative binding studies established a two-step lipid-partitioning/transporter-binding recognition mechanism.

    Evidence X-ray crystallography of mouse P-gp, site-directed mutagenesis, quantitative binding assays with 39 compounds

    PMID:25640267 PMID:26381710

    Open questions at the time
    • Human P-gp high-resolution structure not yet available at this time
    • Outward-facing drug-release conformation not captured crystallographically
  11. 2015 High

    PET imaging with 11C-metoclopramide in living rats demonstrated that P-gp at the BBB actively mediates efflux (not just influx limitation), establishing bidirectional transport in vivo.

    Evidence PET imaging with/without tariquidar inhibition and two-tissue-compartment kinetic modeling

    PMID:26585058

    Open questions at the time
    • Relative contribution of influx limitation vs active efflux for different substrates not quantified
    • Translation to human BBB PET not yet performed
  12. 2019 Medium

    Multiple transcriptional and post-transcriptional regulatory axes were delineated: gut microbiota suppress intestinal ABCB1 via CAR, TGF-β1 upregulates it through the SMAD4/HOTAIR/miR-145 cascade, and STAT5a directly activates ABCB1 transcription in breast cancer.

    Evidence Germ-free/antibiotic mouse models with ABCB1 inhibitor rescue; siRNA knockdowns of SMAD4/HOTAIR/EZH2 with miR-145 reporter assays; STAT5a ChIP and gain/loss-of-function with xenograft validation

    PMID:30698830 PMID:34336684 PMID:37408070

    Open questions at the time
    • Integration of these regulatory inputs in the same cellular context not tested
    • Relative quantitative contribution of each pathway to total ABCB1 expression unknown
    • CAR-binding site in ABCB1 promoter not mapped
  13. 2022 Medium

    USP7 was identified as a deubiquitinase that directly interacts with and stabilizes ABCB1, and CDK6 was shown to regulate ABCB1 through a PI3K-dependent axis involving alternative splicing, revealing post-translational and co-transcriptional control layers.

    Evidence Co-IP, ubiquitination assays, siRNA/inhibitor studies for USP7; CRISPR KO of CDK6/PI3K with transcriptomic and in vivo xenograft validation

    PMID:35459184 PMID:36291159

    Open questions at the time
    • USP7 interaction validated in a single lab; reciprocal IP and structural interface not defined
    • CDK6-dependent splicing mechanism not molecularly characterized
    • Whether USP7 and CDK6 pathways interact is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the precise structural mechanism coupling drug binding to the NBD power stroke in the human protein, the physiological significance of the tubulin–linker interaction, and how multiple transcriptional/post-translational inputs are integrated to set ABCB1 expression levels in specific tissues.
  • High-resolution cryo-EM structures of human ABCB1 in multiple conformational states with bound clinical substrates needed
  • Functional role of tubulin binding via the linker domain not tested by mutagenesis in transport assays
  • Systems-level integration of regulatory inputs (CAR, STAT5a, miR-145, USP7, CDK6) in primary human tissues not addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 8 GO:0140657 ATP-dependent activity 6 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 6 GO:0005635 nuclear envelope 1 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-382551 Transport of small molecules 8 R-HSA-1643685 Disease 4 R-HSA-9748784 Drug ADME 4
Partners
TUBA1ATUBBUSP7

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The MDR1/ABCB1 gene encodes a 1280 amino acid membrane glycoprotein (P-glycoprotein) consisting of two homologous halves, each with six predicted transmembrane segments and a hydrophilic nucleotide-binding domain homologous to bacterial active transport proteins, consistent with a function as an energy-dependent efflux pump. cDNA sequencing, sequence analysis and homology comparison Cell High 2876781 3768958
1986 Overexpression of a single full-length mdr1 cDNA clone in drug-sensitive cells is sufficient to confer a complete multidrug-resistant phenotype, establishing that ABCB1 alone mediates multidrug resistance. cDNA transfection and drug resistance phenotyping Nature High 3022150
1988 Spontaneous point mutations in the mdr1/ABCB1 gene during colchicine selection result in single amino acid changes in P-glycoprotein that alter the pattern of drug cross-resistance, demonstrating that substrate specificity is encoded within the P-glycoprotein sequence. cDNA sequencing of MDR cells, site-directed mutagenesis, transfection and drug resistance profiling Cell High 2897240
1989 Gp170/P-glycoprotein functions as an ATP-dependent efflux pump for cytotoxic drugs (daunomycin) in rat liver canalicular membrane vesicles; transport requires ATP hydrolysis (non-hydrolyzable analogues are ineffective), is temperature-dependent, osmotically sensitive, saturable, and occurs only in inside-out vesicles, indicating unidirectional (cytoplasm-to-lumen) drug transport. Canalicular membrane vesicle transport assays, antibody-induced affinity density perturbation to separate inside-out from right-side-out vesicles, ATP analogue competition The Journal of biological chemistry High 2568355
1992 Gp170/P-glycoprotein in rat small intestinal brush border membrane vesicles functions as an ATP-dependent efflux pump transporting substrates (daunomycin, rhodamine 123) unidirectionally from cytoplasm into the intestinal lumen; non-hydrolyzable ATP analogues are ineffective, demonstrating that ATP hydrolysis is required. Brush border membrane vesicle transport assays, everted intestinal sac transport experiments, P-gp inhibitor studies Gastroenterology High 1347031
1996 MDR1 P-glycoprotein (ABCB1) functions as a broad-specificity lipid translocase, translocating short-chain analogs of various membrane lipids (phosphatidylcholine, sphingomyelin, glucosylceramide, phosphatidylethanolamine) to the apical membrane leaflet, while MDR3 P-gp specifically translocates phosphatidylcholine, establishing a lipid flippase activity for ABCB1. Stable transfection of LLC-PK1 epithelial cells, short-chain fluorescent lipid analogue translocation assays at 15°C (no vesicular secretion), MDR inhibitor and energy depletion controls Cell High 8898203
2000 A synonymous polymorphism in exon 26 (C3435T) of MDR1/ABCB1 significantly correlates with intestinal P-glycoprotein expression levels and function (digoxin absorption), demonstrating that this SNP or a linked variant modulates P-gp expression and substrate pharmacokinetics in vivo. Sequencing of MDR1 in volunteers, Western blot and quantitative immunohistology of duodenal P-gp, oral digoxin plasma level measurements Proceedings of the National Academy of Sciences of the United States of America High 10716719
2001 The MDR1*2 haplotype (C1236T/G2677T/C3435T) carrying Ser893 in exon 21 shows enhanced digoxin efflux in vitro and is associated with altered fexofenadine pharmacokinetics in vivo, identifying functionally variant ABCB1 alleles that differ in substrate transport efficiency. In vitro expression of MDR1 alleles with Ala893 vs Ser893, digoxin efflux assay, fexofenadine pharmacokinetics in human subjects stratified by genotype Clinical pharmacology and therapeutics High 11503014
2003 Substrate recognition by P-glycoprotein occurs within the transmembrane domains at multiple overlapping binding sites; the protein hydrolyzes two ATPs per molecule of drug transported, with conformational changes in the transmembrane domains driven by ATP hydrolysis coupling energy to drug efflux. Biochemical assays, site-directed mutagenesis, photoaffinity labeling, ATPase activity measurements (review synthesizing multiple primary studies) Oncogene High 14576852
2005 P-glycoprotein deficiency at the blood-brain barrier leads to significantly reduced clearance of Aβ40 and Aβ42 from the CNS and increased amyloid deposition in APP-transgenic mice, establishing a direct mechanistic role for ABCB1 in Aβ efflux transport across the BBB. Radiolabeled Aβ microinjection into CNS of Pgp-null vs WT mice, P-gp inhibitor administration in APP-transgenic mice, interstitial fluid Aβ measurement, APP-transgenic/Pgp-null crosses with histological amyloid quantification The Journal of clinical investigation High 16239972
2006 A synonymous SNP (C3435T) in MDR1/ABCB1, part of the 1236T-2677T-3435T haplotype, produces P-glycoprotein with altered drug and inhibitor interactions despite similar mRNA and protein levels; the polymorphic P-gp exhibits altered conformation, suggesting that a rare codon slows cotranslational folding and changes the structure of substrate and inhibitor interaction sites. Cell-based expression of wild-type vs. polymorphic P-gp, drug interaction assays, inhibitor interaction studies, conformational analysis Science High 17185560
2006 P-glycoprotein localizes to both luminal and abluminal membranes of brain capillary endothelial cells as well as to adjacent pericytes and astrocytes; subcellularly it is distributed along the nuclear envelope, in caveolae, cytoplasmic vesicles, Golgi complex, and rough ER, consistent with roles in protein synthesis, glycosylation, membrane trafficking, and drug efflux at multiple BBB cell types. Immunogold cytochemistry at electron microscope level in rat and human brain tissues The journal of histochemistry and cytochemistry Medium 16801529
2007 ATP binding at the interface of the two nucleotide-binding domains (NBDs) of P-glycoprotein induces formation of a closed NBD dimer, and the power-stroke for drug transport is provided only after formation of the pre-hydrolysis transition-like state during ATP hydrolysis; this catalytic mechanism couples NBD dimerization and ATP hydrolysis to conformational changes in the transmembrane domains that drive drug efflux. Mutational analysis of NBDs, biochemical ATP hydrolysis assays, structural studies with isolated NBDs, review synthesizing mechanistic data Molecular cancer therapeutics High 17237262
2007 The linker domain of human ABCB1 (approximately 90 amino acids connecting the two halves) contains three polypeptide sequences (LDS617-627, LDS657-676, LDS693-705) that directly bind alpha- and beta-tubulins (identified as a ~57 kDa protein), providing the first evidence that ABCB1 interacts with intracellular cytoskeletal proteins via its linker domain. Overlapping hexapeptide binding assay spanning the linker domain, affinity purification, N-terminal amino acid sequencing, Western blot with anti-tubulin antibodies Biochemistry Medium 17530867
2009 Pro-inflammatory cytokines TNF-α increases P-glycoprotein mRNA and protein expression at the blood-brain barrier (hCMEC/D3 cells), while IL-6 slightly reduces it; these changes suggest inflammatory signaling regulates ABCB1 expression at the BBB. Cytokine treatment of hCMEC/D3 cells, qRT-PCR, Western blot, functional rhodamine 123 uptake assay Cellular and molecular neurobiology Medium 19629677
2011 Sildenafil inhibits the drug efflux function of ABCB1 by stimulating its ATPase activity and competitively inhibiting photoaffinity labeling with [125I]-IAAP at the substrate-binding site, increasing intracellular concentration of ABCB1 substrate drugs (paclitaxel) in ABCB1-overexpressing cells; sildenafil does not alter ABCB1 protein expression. Cytotoxicity assays in ABCB1-overexpressing cells, intracellular drug accumulation measurements, ATPase activity assay, [125I]-IAAP photoaffinity labeling competition, homology modeling Cancer research High 21402712
2014 P-glycoprotein was functionally reconstituted in giant proteoliposomes; active transport of rhodamine 123 required ATP (absent with verapamil or without ATP), and kinetic modeling revealed passive diffusion and active transport rate constants; patch-clamp on giant proteoliposomes also identified co-purifying chloride ion channel activity. Hydrogel-assisted reconstitution in giant proteoliposomes, fluorescence-based transport quantification, kinetic modeling, patch-clamp electrophysiology Biochimica et biophysica acta High 25450342
2015 ABCB1 exhibits structural flexibility in its inward-facing conformation (shown by multiple X-ray crystal structures with varying degrees of domain separation), and site-directed mutagenesis reveals multiple transport-active substrate binding sites within a large common drug-binding pocket, explaining the molecular basis of polyspecificity. X-ray crystallography (mouse P-gp), site-directed mutagenesis, biochemical and biophysical studies, molecular modeling Advances in cancer research High 25640267
2015 ABCB1 and ABCG2 bind their allocrites (substrates) from the lipid membrane via a two-step mechanism: lipid-water partitioning driven by hydrophobic interactions, followed by transporter binding in the lipid bilayer driven by hydrogen bond acceptors in the substrate; the number of H-bond donors is higher in ABCG2 than ABCB1, explaining their different substrate affinities. Quantitative binding assays with 39 diverse compounds, transporter structural analysis, identification of H-bond donor residues in translocation pathways Biochemistry Medium 26381710
2015 PET imaging with 11C-metoclopramide demonstrated that ABCB1 (P-gp) at the blood-brain barrier not only reduces drug influx into the brain but also actively mediates efflux from the brain back to blood (increased efflux rate constant k2 after P-gp inhibition with tariquidar), establishing a bidirectional transport role for ABCB1 at the BBB. 11C-metoclopramide PET imaging in rats with/without tariquidar P-gp inhibition, 2-tissue-compartment kinetic modeling, in vitro P-gp/BCRP transport assays Journal of nuclear medicine High 26585058
2019 Gut microbiota downregulates ABCB1 expression in the small intestine through polar bacterial metabolites and the Constitutive Androstane Receptor (CAR) transcription factor, thereby increasing tacrolimus bioavailability; antibiotic-mediated reduction of gut microbial load increases intestinal ABCB1 expression and reduces tacrolimus blood levels, while ABCB1 inhibition with zosuquidar abolishes this effect. Antibiotic-treated and germ-free mouse models, conventionalization experiments, in vivo zosuquidar ABCB1 inhibition, bacterial metabolite treatment, whole transcriptome analysis, in vitro microbiota-conditioned medium experiments Microbiome High 37408070
2022 USP7 (ubiquitin specific protease 7) is a deubiquitinating enzyme that directly interacts with ABCB1, stabilizes it by removing ubiquitin, and thereby increases ABCB1 protein levels and chemoresistance; USP7 knockdown reduces ABCB1 protein stability and sensitizes chemoresistant TNBC cells to doxorubicin. Co-immunoprecipitation, Western blot (ubiquitination assay), siRNA knockdown, USP7 inhibitor, overexpression, cell viability and apoptosis assays Cells Medium 36291159
2022 CDK6 regulates ABCB1 expression through a CDK6-PI3K signaling axis; CDK6 knockout in KB-C2 cells dramatically downregulates ABCB1 mRNA and protein and reverses ABCB1-mediated MDR; this involves CDK6-dependent alternative splicing of premature ABCB1 mRNA, and CDK6 and PI3K110α/β act synergistically to regulate ABCB1 levels. CRISPR/Cas9 knockout of CDK6/CDK4/PI3K110α/110β, Western blot, RT-PCR, transcriptome analysis, flow cytometry, in vivo xenograft tumor experiments Molecular cancer Medium 35459184
2019 TGF-β1 upregulates P-glycoprotein (ABCB1) expression in hepatocellular carcinoma cells via a SMAD4/HOTAIR/miR-145 axis: TGF-β1 activates SMAD4 to induce HOTAIR lncRNA, which recruits EZH2 to suppress miR-145, and miR-145 directly suppresses ABCB1 translation by binding to the 3'-UTR of ABCB1 mRNA. siRNA knockdown of SMAD4/HOTAIR/EZH2, miR-145 overexpression/inhibition, luciferase 3'-UTR reporter assay (implied), Western blot, RT-PCR Biopharmaceutics & drug disposition Medium 30698830
2001 P-glycoprotein expression in multidrug-resistant CEM/VBL100 cells sensitizes them specifically to mitochondria-mediated apoptosis (induced by TNF-α and staurosporine) correlated with mitochondrial membrane hyperpolarization, while simultaneously conferring resistance to Fas/CD95 and etoposide-induced apoptosis, revealing that ABCB1 expression shifts cell death pathways from plasma membrane-associated (type I) to mitochondria-associated (type II) apoptosis. Cell death assays with multiple proapoptotic stimuli, mitochondrial membrane potential measurement, MDR cell line comparison The Biochemical journal Medium 11311119
2019 ABCB1 is expressed at higher levels in multiple bat cell lines and tissues compared to human and mouse; efficient ABCB1-mediated drug efflux protects bat cells from DNA damage induced by genotoxic compounds (doxorubicin), as ABCB1 inhibition restores doxorubicin accumulation, DNA damage, and cell death in bat cells. Drug accumulation assays, ABCB1 inhibitor experiments, Western blot, DNA damage assays, cell death assays across multiple bat species cell lines Nature communications Medium 31249297
2019 STAT5a transcription factor directly regulates ABCB1 transcription in breast cancer, with STAT5a and ABCB1 expression positively correlated; STAT5a knockdown reduces ABCB1 expression and doxorubicin resistance, and STAT5a overexpression increases ABCB1-mediated resistance. Western blot, ChIP or transcriptional reporter assay, siRNA knockdown, overexpression, in vivo xenograft experiments Frontiers in oncology Medium 34336684
2013 Methadone acts as a non-competitive inhibitor of wild-type human P-glycoprotein (IC50 = 2.17 μM) and also stimulates P-gp ATPase activity; variant P-gp bearing the 1236T-2677T-3435T haplotype (or 1236T-2677A-3435T) shows reduced inhibition potency (IC50 = 2.97–4.43 μM) via uncompetitive kinetics, explaining higher methadone dose requirements in variant carriers. Stably transfected Flp-In-293 cells expressing wild-type or variant P-gp, rhodamine 123 efflux assay, calcein-AM uptake assay, P-gp ATPase assay, enzyme kinetic analysis PloS one Medium 23527191
2003 Doxorubicin selectively induces mdr1b (but not mdr1a or mrp1) mRNA expression in rat astrocyte primary cultures in a time- and dose-dependent manner that is inhibited by actinomycin D, indicating transcriptional upregulation; the induced P-gp is functionally active, enhancing vincristine efflux that is blocked by P-gp inhibitors (PSC833, GW918) but not by the MRP1 inhibitor MK571. Northern blot (mRNA), Western blot (protein), functional vincristine efflux assay with selective inhibitors in primary rat astrocyte cultures Journal of neurochemistry Medium 14622113

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 1895 2876781
2006 A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science (New York, N.Y.) 1887 17185560
2000 Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proceedings of the National Academy of Sciences of the United States of America 1772 10716719
2019 Blood-Brain Barrier: From Physiology to Disease and Back. Physiological reviews 1645 30280653
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2008 Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine 1335 19106083
2015 Establishment and Dysfunction of the Blood-Brain Barrier. Cell 1304 26590417
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1986 Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 1021 3768958
2003 P-glycoprotein: from genomics to mechanism. Oncogene 869 14576852
2001 Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clinical pharmacology and therapeutics 836 11503014
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
1986 Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 814 3022150
1996 MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 751 8898203
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet (London, England) 634 20801498
2001 Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clinical pharmacology and therapeutics 626 11240981
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2003 Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clinical pharmacology and therapeutics 579 12966368
2005 P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. The Journal of clinical investigation 541 16239972
2002 Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet (London, England) 530 11809184
2004 Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS (London, England) 516 15622315
2003 Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. The New England journal of medicine 484 12686700
2010 Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet (London, England) 483 20801494
2001 Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. The Journal of pharmacology and experimental therapeutics 448 11356939
1988 An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell 436 2897240
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2002 Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. The Journal of biological chemistry 430 12493773
2012 Three decades of P-gp inhibitors: skimming through several generations and scaffolds. Current medicinal chemistry 417 22257057
1997 Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. Journal of the National Cancer Institute 351 9214671
1989 The function of Gp170, the multidrug resistance gene product, in rat liver canalicular membrane vesicles. The Journal of biological chemistry 312 2568355
2007 Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clinical pharmacology and therapeutics 245 17898703
2005 Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 175 16143395
2005 The power of the pump: mechanisms of action of P-glycoprotein (ABCB1). European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 168 16352426
2006 In situ localization of P-glycoprotein (ABCB1) in human and rat brain. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 166 16801529
2009 Regulation of BCRP (ABCG2) and P-glycoprotein (ABCB1) by cytokines in a model of the human blood-brain barrier. Cellular and molecular neurobiology 144 19629677
2011 Sildenafil reverses ABCB1- and ABCG2-mediated chemotherapeutic drug resistance. Cancer research 143 21402712
2004 Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Therapeutic drug monitoring 143 15228162
1992 The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Gastroenterology 141 1347031
2004 The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clinical pharmacokinetics 124 15217301
2007 About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work. Molecular cancer therapeutics 121 17237262
2019 Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer. Frontiers in oncology 119 31921655
2015 Molecular basis of the polyspecificity of P-glycoprotein (ABCB1): recent biochemical and structural studies. Advances in cancer research 111 25640267
2013 Inhibition of ABCB1 expression overcomes acquired docetaxel resistance in prostate cancer. Molecular cancer therapeutics 111 23861346
2008 Genuine functions of P-glycoprotein (ABCB1). Current drug metabolism 111 18288958
2012 Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation. The EMBO journal 107 22549467
2007 ABCB1 pharmacogenetics: progress, pitfalls, and promise. Clinical pharmacology and therapeutics 105 17259950
2004 Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharmaceutical research 98 15212152
2005 Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection. Biology of reproduction 86 15917342
2018 Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells. Cancer letters 84 30315846
2007 Both P-gp and MRP2 mediate transport of Lopinavir, a protease inhibitor. International journal of pharmaceutics 84 17451894
2007 Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats. Journal of pharmaceutical sciences 82 17593551
2009 Recent advances in the development of P-gp inhibitors. Anti-cancer agents in medicinal chemistry 81 19442042
2007 Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene. Pharmacogenomics 79 17187507
2013 Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib, and dasatinib. Clinical pharmacology and therapeutics 73 24107928
2013 MDR1 (ABCB1) polymorphisms: functional effects and clinical implications. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 73 24687344
2005 Modulation of drug transport by selected flavonoids: Involvement of P-gp and OCT? European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 72 15911222
2004 Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms. Pharmacogenetics 72 15247630
2010 ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression. Pharmacogenetics and genomics 71 20555295
1997 Circumvention of P-GP MDR as a function of anthracycline lipophilicity and charge. Biochemistry 69 9054575
2006 MDR1/P-glycoprotein (ABCB1) as target for RNA interference-mediated reversal of multidrug resistance. Current drug targets 68 16842213
2015 Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter. Oncotarget 63 25915534
2011 Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice. International journal of Alzheimer's disease 62 21660212
2007 Genomics and the mechanism of P-glycoprotein (ABCB1). Journal of bioenergetics and biomembranes 62 18058211
2023 Genetics of ABCB1 in Cancer. Cancers 60 37686513
2019 Tetrandrine Interaction with ABCB1 Reverses Multidrug Resistance in Cancer Cells Through Competition with Anti-Cancer Drugs Followed by Downregulation of ABCB1 Expression. Molecules (Basel, Switzerland) 54 31801248
2019 Tepotinib reverses ABCB1-mediated multidrug resistance in cancer cells. Biochemical pharmacology 53 31078601
2016 Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9. Journal of pharmaceutical sciences 53 26869442
2015 Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives. European journal of medicinal chemistry 50 26197160
2014 Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on postoperative morphine consumption. Basic & clinical pharmacology & toxicology 50 24703092
2007 Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) II. Clinical aspects. Drug discovery today 50 17933685
2017 P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer's Disease. Oxidative medicine and cellular longevity 49 29317984
2022 CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells. Molecular cancer 48 35459184
2015 Imaging the Impact of the P-Glycoprotein (ABCB1) Function on the Brain Kinetics of Metoclopramide. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 48 26585058
2016 Ferulic acid reverses ABCB1-mediated paclitaxel resistance in MDR cell lines. European journal of pharmacology 47 27262378
2009 ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer. International journal of colorectal disease 45 19415305
2019 TGF-β1 elevates P-gp and BCRP in hepatocellular carcinoma through HOTAIR/miR-145 axis. Biopharmaceutics & drug disposition 44 30698830
2008 Human pharmaceuticals modulate P-gp1 (ABCB1) transport activity in the fish cell line PLHC-1. Aquatic toxicology (Amsterdam, Netherlands) 44 18950875
2023 Gut microbiome modulates tacrolimus pharmacokinetics through the transcriptional regulation of ABCB1. Microbiome 43 37408070
2012 Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicology and applied pharmacology 43 22464980
2020 Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies. International journal of molecular sciences 42 32517082
2020 Sitravatinib Sensitizes ABCB1- and ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Chemotherapeutic Drugs. Cancers 41 31941029
2019 ABCB1 protects bat cells from DNA damage induced by genotoxic compounds. Nature communications 41 31249297
2019 Drug-Drug Interactions of P-gp Substrates Unrelated to CYP Metabolism. Current drug metabolism 39 30280663
2019 Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. Journal of psychopharmacology (Oxford, England) 39 30789308
2021 Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers. Bioscience reports 38 33543229
2009 Association of a polymorphism in the ABCB1 gene with Parkinson's disease. Parkinsonism & related disorders 38 19196542
2008 Canine ABCB1 and macrocyclic lactones: heartworm prevention and pharmacogenetics. Veterinary parasitology 38 18922637
2021 Structure-Function Relationships in the Human P-Glycoprotein (ABCB1): Insights from Molecular Dynamics Simulations. International journal of molecular sciences 37 35008783
2016 An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure. The pharmacogenomics journal 37 27897269
2015 Lipid regulation of the ABCB1 and ABCG2 multidrug transporters. Advances in cancer research 37 25640268
2017 Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo. Experimental & molecular medicine 36 28303028
2013 Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone. PloS one 36 23527191
2009 P-glycoprotein (ABCB1) modulates collateral sensitivity of a multidrug resistant cell line to verapamil. Archives of biochemistry and biophysics 36 19772851
2019 Ciprofloxacin Enhances the Chemosensitivity of Cancer Cells to ABCB1 Substrates. International journal of molecular sciences 34 30641875
2016 ABCB1 and ABCC11 confer resistance to eribulin in breast cancer cell lines. Oncotarget 33 27588398
2010 Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study. Neuropsychobiology 32 20664232
2007 Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) I. Preclinical aspects. Drug discovery today 32 17933684
2019 Clinical Significance of ABCB1 in Acute Myeloid Leukemia: A Comprehensive Study. Cancers 31 31500210
2017 The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors. Molecular cancer therapeutics 31 28265007
2011 P-glycoprotein (ABCB1) expression in human skin is mainly restricted to dermal components. Experimental dermatology 31 21366702
2020 Expression of P-gp in Glioblastoma: What we can Learn from Brain Development. Current pharmaceutical design 29 32186270
2016 Gene Therapeutic Approaches to Overcome ABCB1-Mediated Drug Resistance. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 29 28101689
2020 Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance. Frontiers in pharmacology 28 32903706
2017 Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells. European journal of medicinal chemistry 28 28189906
2014 ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. The pharmacogenomics journal 28 25487678
2007 The P-glycoprotein (ABCB1) linker domain encodes high-affinity binding sequences to alpha- and beta-tubulins. Biochemistry 28 17530867
2013 ABCB6, ABCB1 and ABCG1 genetic polymorphisms and antidepressant response of SSRIs in Chinese depressive patients. Pharmacogenomics 27 24192121
2022 USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1. Cells 26 36291159
2017 Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance. International journal of oncology 26 28534954
2014 Cyclosporin A affects the bioavailability of ginkgolic acids via inhibition of P-gp and BCRP. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 26 24980806
2009 CYP3A5 and ABCB1 genes and hypertension. Pharmacogenomics 26 19290795
2016 ABCB1 1199G>A polymorphism (rs2229109) affects the transport of imatinib, nilotinib and dasatinib. Pharmacogenomics 25 27268766
2015 Allocrite Sensing and Binding by the Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1). Biochemistry 25 26381710
2014 Cargoing P-gp inhibitors via nanoparticle sensitizes tumor cells against doxorubicin. International journal of pharmaceutics 25 25437111
2003 P-glycoprotein (ABCB1) but not multidrug resistance-associated protein 1 (ABCC1) is induced by doxorubicin in primary cultures of rat astrocytes. Journal of neurochemistry 25 14622113
2021 Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer. PloS one 24 34347777
2015 Identification of a nonsense mutation in feline ABCB1. Journal of veterinary pharmacology and therapeutics 24 25660379
2014 Hydrogel-assisted functional reconstitution of human P-glycoprotein (ABCB1) in giant liposomes. Biochimica et biophysica acta 24 25450342
2012 The two enantiomers of tetrahydropalmatine are inhibitors of P-gp, but not inhibitors of MRP1 or BCRP. Xenobiotica; the fate of foreign compounds in biological systems 24 22900779
2021 STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1. Frontiers in oncology 23 34336684
2014 Impact of common ABCB1 polymorphism on pharmacokinetics and pharmacodynamics of clopidogrel and its metabolites. Journal of clinical pharmacy and therapeutics 23 25430046
2013 Rilpivirine inhibits drug transporters ABCB1, SLC22A1, and SLC22A2 in vitro. Antimicrobial agents and chemotherapy 23 24002095
2007 Promoter polymorphisms and allelic imbalance in ABCB1 expression. Pharmacogenetics and genomics 23 18075465
2001 Expression of P-170 glycoprotein sensitizes lymphoblastoid CEM cells to mitochondria-mediated apoptosis. The Biochemical journal 23 11311119
2021 Dietary bioactive diindolylmethane enhances the therapeutic efficacy of centchroman in breast cancer cells by regulating ABCB1/P-gp efflux transporter. The Journal of nutritional biochemistry 22 33910062
2015 OPRM1 and ABCB1 polymorphisms and their effect on postoperative pain relief with piritramide. Physiological research 22 26681082
2021 Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents. Pharmaceutics 21 33921129