Affinage

ABCB1

ATP-dependent translocase ABCB1 · UniProt P08183

Length
1280 aa
Mass
141.5 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCB1 (P-glycoprotein/Gp170) is an ATP-dependent efflux pump that drives vectorial export of structurally diverse hydrophobic substrates across membranes at tissue barriers (PMID:2568355, PMID:1347031, PMID:15640379). It couples ATP binding and hydrolysis at a closed dimer of its two nucleotide-binding domains to a 'twist-and-squeeze' conformational cycle, transitioning between inward- and outward-facing states to expel substrate to the extracellular space, as resolved by crystal structures of pre- and post-transport states and confirmed by FRET in living cells (PMID:17237262, PMID:33275773); a large, polyspecific drug-binding pocket within the transmembrane domains contains overlapping primary and secondary sites that accommodate multiple substrates, accounting for its broad specificity (PMID:25640267, PMID:21402712). Functionally, ABCB1 establishes barrier and protective roles at the liver canaliculus, intestinal brush border, placental syncytiotrophoblast, and blood-brain barrier, where it restricts oral uptake and brain penetration of xenobiotics and drugs (PMID:2568355, PMID:1347031, PMID:15640379, PMID:20028753, PMID:28111265), and it cooperates with LRP1 (via PICALM) in transcytotic clearance of amyloid-beta across brain endothelium (PMID:30041013). Its abundance is set transcriptionally by nuclear receptors responding to microbial metabolites—gut bacteria downregulate ABCB1 through the Constitutive Androstane Receptor—and by a CDK6/PI3K signaling axis and a TGF-β1/SMAD4/HOTAIR/miR-145 pathway acting on ABCB1 mRNA (PMID:37408070, PMID:35459184, PMID:30698830), while at the protein level it is degraded through the lysosomal pathway and stabilized by the deubiquitinase USP7 (PMID:26057472, PMID:36291159). Beyond transport, ABCB1 maintains extravillous trophoblast invasiveness and suppresses syncytiotrophoblast differentiation, and its expression shifts apoptotic pathway choice toward mitochondria-mediated cell death (PMID:30256530, PMID:11311119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Established that ABCB1/Gp170 is itself an ATP-driven primary active transporter rather than a passive component, by demonstrating energized, vectorial drug efflux in defined membrane vesicles.

    Evidence ATP-dependent daunomycin transport in rat liver canalicular inside-out vesicles with non-hydrolyzable analogue and inhibitor controls

    PMID:2568355

    Open questions at the time
    • Did not resolve the structural basis of transport
    • Substrate range and binding-site architecture not defined
  2. 1992 High

    Extended the efflux function to an epithelial barrier role, showing ABCB1 acts as an intestinal gate against hydrophobic xenobiotics.

    Evidence ATP-dependent transport in rat intestinal brush border vesicles plus everted intestine directional transport of rhodamine 123

    PMID:1347031

    Open questions at the time
    • Quantitative contribution to oral bioavailability in vivo not addressed
    • Did not identify regulatory inputs
  3. 2001 Medium

    Revealed a non-transport function: ABCB1 expression reprograms apoptotic pathway choice toward mitochondria-mediated death.

    Evidence Comparison of P-170-expressing VBL100 vs wild-type CEM cells across multiple proapoptotic stimuli with mitochondrial membrane potential measurement

    PMID:11311119

    Open questions at the time
    • Molecular mechanism linking P-gp to mitochondrial polarization unknown
    • Single cell-line pair
  4. 2005 High

    Confirmed functional ABCB1 efflux activity at the placental syncytiotrophoblast, supporting a fetal-protective barrier.

    Evidence ATP-dependent, osmotically sensitive, verapamil-inhibitable vinblastine uptake in human placental vesicles with immunohistochemistry

    PMID:15640379

    Open questions at the time
    • Relative contribution vs other placental transporters not quantified
  5. 2006 Medium

    Mapped ABCB1 to luminal and abluminal BBB endothelial membranes plus biosynthetic and trafficking compartments, framing it as a regulator of brain drug distribution.

    Evidence Immunogold electron microscopy in situ in rat and human brain

    PMID:16801529

    Open questions at the time
    • Functional significance of bilateral and intracellular pools not tested
    • Single lab
  6. 2007 Medium

    Defined the ATP hydrolysis cycle as the power source, identifying the closed NBD dimer and pre-hydrolysis transition state as the power-stroke.

    Evidence NBD mutagenesis and ATPase assays synthesized with structural studies (review)

    PMID:17237262

    Open questions at the time
    • Review synthesis rather than single primary experiment
    • Coupling to substrate movement not directly visualized here
  7. 2007 Medium

    Identified a direct physical interaction between the ABCB1 linker domain and alpha/beta-tubulin, linking the pump to the cytoskeleton.

    Evidence Overlapping hexapeptide binding, protein purification, N-terminal sequencing and anti-tubulin Western blot

    PMID:17530867

    Open questions at the time
    • No functional consequence of tubulin binding established
    • In vitro peptide interaction only
  8. 2009 High

    Used genetic epistasis to assign ABCB1 a specific role in intestinal etoposide efflux, distinct from hepatobiliary excretion handled by Abcc2.

    Evidence Single and combination Abcb1a/1b, Abcc2, Abcc3 knockout mouse pharmacokinetics

    PMID:20028753

    Open questions at the time
    • Human translation of transporter division of labor not addressed
  9. 2011 High

    Demonstrated that inhibitors such as sildenafil act within the drug-binding pocket to reverse ABCB1-mediated resistance, validating the transmembrane pocket as a pharmacological target.

    Evidence ATPase stimulation, competitive [125I]-IAAP photolabeling, drug accumulation and cytotoxicity reversal assays

    PMID:21402712

    Open questions at the time
    • Exact residues contacted not resolved
    • Specificity over other ABC transporters only partially tested
  10. 2013 Medium

    Showed that ABCB1 coding haplotypes alter the kinetic mechanism of drug interaction, establishing that genotype reshapes pump pharmacology.

    Evidence Stable expression of defined P-gp genotypes with rhodamine/calcein efflux, ATPase and kinetic analysis using methadone

    PMID:23527191

    Open questions at the time
    • Clinical pharmacokinetic consequences not measured
    • Limited to specific haplotypes/substrate
  11. 2015 High

    Provided structural and mutational evidence for conformational flexibility and a single large polyspecific binding pocket with overlapping sites, explaining substrate promiscuity.

    Evidence Multiple inward-facing mouse P-gp crystal structures with site-directed mutagenesis and SAR (review/primary structural work)

    PMID:25640267

    Open questions at the time
    • Outward-facing transition not captured in these structures
    • Mouse rather than human protein
  12. 2015 High

    Identified the lysosome as the primary route of ABCB1 turnover, defining a post-translational determinant of pump abundance.

    Evidence Cell surface biotinylation half-life measurements with lysosomal/proteasomal inhibitors and LAMP1 co-localization

    PMID:26057472

    Open questions at the time
    • Ubiquitin/trafficking signals routing P-gp to lysosomes not defined here
  13. 2018 Medium

    Placed ABCB1 in a cooperative amyloid-beta clearance pathway with LRP1, physically linked by PICALM at the BBB.

    Evidence Immunoprecipitation, co-immunostaining and dual ABCB1/LRP1 inhibition with Aβ transport assay

    PMID:30041013

    Open questions at the time
    • Direct vs indirect nature of the ABCB1-PICALM-LRP1 association unresolved
    • Single lab
  14. 2018 Medium

    Revealed a transport-independent developmental role: ABCB1 maintains extravillous trophoblast invasiveness and suppresses syncytiotrophoblast differentiation.

    Evidence siRNA knockdown in HTR8/SVneo with invasion, migration, fusion, tube formation and differentiation-marker assays

    PMID:30256530

    Open questions at the time
    • Molecular effector downstream of P-gp not identified
    • Cell-line model
  15. 2019 Medium

    Dissected transcriptional and mRNA-level control of ABCB1, identifying microbiota/CAR, CDK6/PI3K, and TGF-β1/SMAD4/HOTAIR/miR-145 inputs.

    Evidence In vivo microbiota depletion/conventionalization with CAR identification; CRISPR CDK6 knockout with splicing/transcriptome analysis; sequential siRNA dissection with 3'-UTR reporter

    PMID:30698830 PMID:35459184 PMID:37408070

    Open questions at the time
    • Direct receptor binding to ABCB1 promoter not all resolved
    • Cross-talk among these pathways unknown
  16. 2019 High

    Quantitatively linked tissue-specific ABCB1 protein abundance to differential barrier function, with strong brain but minor placental restriction of norbuprenorphine.

    Evidence Abcb1a/1b knockout mouse tissue pharmacokinetics with LC-MS/MS protein quantification

    PMID:28111265

    Open questions at the time
    • Human placental relevance not directly tested
  17. 2019 High

    Established a recombinant purification and reconstitution platform, confirming the isolated protein is a functional ATPase and enabling hydrolysis-deficient mutant studies.

    Evidence Baculovirus expression, IMAC/SEC purification, proteoliposome/nanodisc reconstitution with ATPase assays and E556Q/E1201Q Walker B mutant

    PMID:30851394

    Open questions at the time
    • Does not by itself define a transport mechanism
  18. 2019 Medium

    Connected ABCB1 efflux to cellular drug/genotoxin resistance and to retention of antiretroviral and chemotherapeutic agents in physiological cell types.

    Evidence Pharmacological inhibition with drug accumulation, DNA damage and viability readouts in bat cells; raltegravir accumulation in primary CD4+ T cells with XR9051

    PMID:27334660 PMID:31249297

    Open questions at the time
    • Mechanism of elevated ABCB1 expression in these contexts only partly defined
  19. 2020 High

    Resolved the transport mechanism at near-atomic detail, showing ATP binding drives a whole-protein twisting that squeezes substrate directly to the extracellular space.

    Evidence High-resolution crystal structures of pre- and post-transport states with FRET in living cells

    PMID:33275773

    Open questions at the time
    • Precise role of hydrolysis vs binding across substrates still debated
    • Dynamics of substrate loading not fully captured
  20. 2022 Medium

    Identified USP7 as a deubiquitinase that directly binds and stabilizes ABCB1, defining a druggable axis controlling pump levels and chemoresistance.

    Evidence Co-immunoprecipitation with USP7 overexpression/knockdown and pharmacological inhibition in TNBC cells

    PMID:36291159

    Open questions at the time
    • Specific ubiquitin sites on ABCB1 not mapped
    • Single lab, Co-IP-based interaction

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ABCB1's transport-independent activities (trophoblast identity, apoptotic pathway choice, cytoskeletal linkage) mechanistically arise and integrate with its canonical efflux function remains unresolved.
  • No molecular effector connecting P-gp to mitochondrial apoptosis or trophoblast differentiation identified
  • Functional role of tubulin binding untested
  • Integration of multiple regulatory pathways controlling ABCB1 abundance not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140657 ATP-dependent activity 6 GO:0016787 hydrolase activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 5 GO:0005764 lysosome 1 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-1643685 Disease 4 R-HSA-9748784 Drug ADME 4 R-HSA-5357801 Programmed Cell Death 1
Partners
LRP1PICALMTUBATUBBUSP7

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Gp170 (ABCB1/P-gp) functions as an ATP-dependent efflux pump in rat liver canalicular membrane vesicles, mediating unidirectional, temperature-dependent, osmotically sensitive, and saturable transport of daunomycin. ATP hydrolysis (not non-hydrolyzable analogues) is required, and transport is inhibited by cytotoxic drugs (vinblastine, vincristine, adriamycin) and verapamil/quinidine. Only inside-out vesicles (cytoplasmic face outward) support transport, establishing vectorial drug efflux into bile. ATP-dependent transport assay in canalicular membrane vesicles; antibody-induced affinity density perturbation to separate inside-out from right-side-out vesicles; inhibitor studies The Journal of biological chemistry High 2568355
1992 Gp170 (ABCB1) in rat small intestinal brush border membrane vesicles (but not basolateral) functions as an ATP-dependent efflux pump transporting daunomycin from inside to outside. Non-hydrolyzable ATP analogues are ineffective. Everted intestine preparations confirm Gp170-mediated serosal-to-mucosal transport of rhodamine 123, inhibitable by Gp170 inhibitors, establishing P-gp as an intestinal barrier against hydrophobic xenobiotics. ATP-dependent transport assay in brush border membrane vesicles; everted intestine transport assay; inhibitor studies; Western blot with anti-Gp170 antibody Gastroenterology High 1347031
2005 ABCB1/P-gp in human placenta is functionally active as an ATP-dependent efflux transporter: ATP-dependent uptake of [3H]vinblastine in placental vesicles is osmotically sensitive (indicating intravesicular accumulation) and inhibited by verapamil. The protein is expressed at high levels and localized to the syncytiotrophoblast, consistent with a fetal-protective barrier role. ATP-dependent vesicle transport assay with [3H]vinblastine; verapamil inhibition; Western blotting; immunohistochemistry Drug metabolism and disposition High 15640379
2006 In human and rat brain, P-gp (ABCB1) localizes to both luminal and abluminal membranes of capillary endothelial cells, as well as to adjacent pericytes and astrocytes. Subcellularly, P-gp is distributed in caveolae, cytoplasmic vesicles, Golgi complex, rough ER, and nuclear envelope, indicating sites of synthesis, glycosylation, and membrane trafficking. Bilateral membrane localization suggests P-gp regulates drug transport processes across the entire BBB. Immunogold cytochemistry at electron microscope level in situ in rat and human brain tissue The journal of histochemistry and cytochemistry Medium 16801529
2007 The linker domain of human ABCB1 (approximately 90 amino acid region connecting the two halves) contains sequences that directly bind alpha- and beta-tubulins. Three polypeptide sequences (LDS617-627, LDS657-676, LDS693-705) interact with a ~57 kDa protein identified by N-terminal sequencing and anti-tubulin Western blot as alpha- and beta-tubulin, establishing a direct protein-protein interaction between ABCB1 and cytoskeletal components. Overlapping hexapeptide binding assay; protein purification; N-terminal amino acid sequencing; Western blot with anti-tubulin monoclonal antibodies Biochemistry Medium 17530867
2007 ATP hydrolysis cycle of P-gp (ABCB1): ATP binds at the interface of the two nucleotide-binding domains (NBDs), inducing formation of a closed NBD dimer; this dimerization and subsequent ATP hydrolysis power drug transport. The power-stroke is provided specifically upon formation of the pre-hydrolysis transition-like (E·S) state during ATP hydrolysis, not simply from ATP binding alone. Mutational analysis of NBDs combined with biochemical ATPase assays; reviewed in conjunction with structural studies of isolated NBDs Molecular cancer therapeutics Medium 17237262
2011 Sildenafil inhibits ABCB1 transport function by stimulating ABCB1 ATPase activity and competitively inhibiting photolabeling of ABCB1 with [125I]-iodoarylazidoprazosin (IAAP), indicating it binds within the drug-binding pocket of ABCB1's transmembrane domain. Sildenafil reverses ABCB1-mediated resistance and increases intracellular accumulation of ABCB1 substrates (paclitaxel). Sildenafil does not affect ABCC1 function. ATPase activity assay; [125I]-IAAP photolabeling/competition assay; intracellular drug accumulation assay; cytotoxicity reversal assay; homology modeling Cancer research High 21402712
2015 ABCB1 (P-gp) exhibits structural flexibility evidenced by multiple X-ray crystal structures of mouse P-gp in inward-facing conformations with different degrees of domain separation, in absence of nucleotide and with bound inhibitors. Site-directed mutagenesis reveals multiple transport-active binding sites for single substrates (primary and secondary sites), with a large common drug-binding pocket with overlapping sites, accounting for polyspecificity. X-ray crystallography of mouse P-gp; site-directed mutagenesis; biochemical and biophysical studies; molecular modeling and SAR analysis Advances in cancer research High 25640267
2015 Cell surface P-gp (ABCB1) is degraded primarily via the lysosomal pathway. Bafilomycin A1 (vacuolar H+ ATPase inhibitor) increased the half-life of P-gp from ~27 h to ~36 h, while proteasomal inhibitors alone had no effect. Combined lysosomal and proteasomal inhibition further extended half-life to 39–50 h. Intracellular P-gp co-localizes with lysosomal marker LAMP1, confirming lysosomal compartment as the primary degradation site. Cell surface biotinylation; flow cytometry; Western blotting; pharmacological inhibitor treatment (BafA1, MG132, MG115, lactacystin); immunofluorescence co-localization with LAMP1 Biochimica et biophysica acta High 26057472
2018 ABCB1/P-gp and LRP1 mediate concerted transcytosis of amyloid-beta (Aβ) across brain endothelial cells at the blood-brain barrier. PICALM (Alzheimer's risk factor) physically associates with both ABCB1/P-gp and LRP1 (shown by immunoprecipitation and co-immunostaining), serving as a functional link guiding both proteins through the brain endothelium. Dual inhibition of ABCB1 and LRP1 demonstrates their cooperative requirement for rapid Aβ clearance. Immunoprecipitation; co-immunostaining; dual pharmacological inhibition of ABCB1 and LRP1; functional Aβ transport assay Brain, behavior, and immunity Medium 30041013
2018 ABCB1/P-gp plays a functional role in extravillous trophoblast (EVT) invasion and migration beyond its transporter role. siRNA silencing of ABCB1 in HTR8/SVneo EVT-like cells dramatically reduces invasion and migration while increasing tube formation, fusion, and induction of syncytiotrophoblast differentiation markers (hCG, ERVW-1, GJA1), demonstrating P-gp maintains trophoblast lineage identity and suppresses terminal differentiation. siRNA knockdown; invasion and migration assays; tube formation assay; trophoblast fusion assay; gene expression analysis of differentiation markers in EVT and CT explants Journal of cellular and molecular medicine Medium 30256530
2019 ABCB1 mediates efficient drug efflux in bat cells, and higher ABCB1 expression underlies bats' superior resistance to DNA damage from genotoxic drugs. Inhibition of ABCB1 with inhibitors triggers accumulation of doxorubicin, increased DNA damage, and cell death in bat cells. ABCB1 expression is conserved at higher levels across multiple bat species compared to human and mouse cells. Pharmacological ABCB1 inhibition; intracellular drug accumulation assay; DNA damage assay; cell viability assay; Western blot; comparison across multiple bat species and cell lines Nature communications High 31249297
2019 Gut microbiota downregulates ABCB1 expression in the small intestine via bacterial metabolites that act on the Constitutive Androstane Receptor (CAR), reducing ABCB1 transcription. This modulation of ABCB1 expression by the microbiome directly affects tacrolimus pharmacokinetics: antibiotic-treated mice with lower microbial load had higher ABCB1 expression and 33% lower tacrolimus blood exposure. Functional ABCB1 inhibition with zosuquidar in vivo confirmed ABCB1 as the mediator. Antibiotic depletion model; germ-free mouse conventionalization; in vivo ABCB1 functional inhibition with zosuquidar; pharmacokinetic analysis; transcriptome analysis; in vitro polar bacterial metabolite experiments; CAR identification Microbiome High 37408070
2019 P-gp/ABCB1 plays a significant role in restricting brain distribution of norbuprenorphine but has only a minor impact on fetal exposure. In Abcb1a/1b knockout mice, maternal brain-to-plasma AUC ratio for norbuprenorphine increased ~30-fold compared to wild-type, while fetal-to-maternal plasma AUC ratio was relatively unchanged. The differential effect is attributed to higher P-gp protein abundance in brain (BBB) versus placenta (blood-placental barrier), quantified by LC-MS/MS proteomics. Abcb1a/1b and Abcb1a/1b/Abcg2 knockout mouse models; pharmacokinetic tissue distribution analysis; LC-MS/MS protein quantification in tissues Pharmacological research High 28111265
2009 P-gp (Abcb1/ABCB1) restricts oral (re)uptake of etoposide and mediates its excretion across the gut wall, established using Abcb1a/1b knockout mice. This was distinct from hepatobiliary excretion, which was almost entirely dependent on Abcc2. In vivo etoposide pharmacokinetics in knockout mouse combinations delineated the separate contributions of P-gp, Abcc2, and Abcc3 to etoposide disposition. Abcb1a/1b(-/-), Abcc2(-/-), Abcc3(-/-) single and combination knockout mice; in vivo pharmacokinetic analysis of etoposide and etoposide glucuronide Clinical cancer research High 20028753
2020 ABCB1 employs an ATP-dependent 'twist-and-squeeze' mechanism to export hydrophobic substrates. High-resolution X-ray crystal structures of pre- and post-transport states reveal that an aromatic hydrophobic network at the top of the inner cavity is critical for conformational change triggered by substrate. ATP binding (not hydrolysis) drives a twisting motion of the whole protein, squeezing out substrate directly to the extracellular space. FRET analyses in living cells confirmed this conformational mechanism. High-resolution X-ray crystallography of pre- and post-transport states; FRET analyses in living cells FEBS letters High 33275773
2022 CDK6 and PI3K (110α/110β) form a signaling axis that synergistically regulates ABCB1 expression. CRISPR/Cas9 knockout of CDK6 in KB-C2 cells led to downregulation of PI3K 110α/110β, KRAS, and MAPK10, and dramatically reduced ABCB1 expression reversing ABCB1-mediated MDR. PI3K 110α/110β deficiency in turn downregulated CDK6. CDK6-induced changes in ABCB1 levels involve alternative splicing of premature ABCB1 mRNA, with 10 common skipped exon events identified. CRISPR/Cas9 knockout of CDK6 or CDK4; Western blot; RT-PCR; transcriptome analysis; flow cytometry; in vivo xenograft models; alternative splicing analysis Molecular cancer Medium 35459184
2022 USP7 is a deubiquitinating enzyme for ABCB1 that directly interacts with ABCB1 and stabilizes the protein, thereby promoting chemoresistance. USP7 overexpression increased ABCB1-dependent chemoresistance in TNBC cells, while USP7 knockdown reduced chemoresistance. The interaction was demonstrated by co-immunoprecipitation, and USP7 inhibitor induced apoptosis and suppressed metastasis in chemoresistant TNBC. Co-immunoprecipitation; USP7 overexpression and siRNA knockdown; cytotoxicity assays; USP7 pharmacological inhibitor; apoptosis and migration assays Cells Medium 36291159
2019 TGF-β1 upregulates ABCB1 (P-gp) expression in hepatocellular carcinoma cells through the SMAD4/HOTAIR/miR-145 axis: TGF-β1 induces HOTAIR lncRNA in a SMAD4-dependent manner; HOTAIR suppresses miR-145 through EZH2; miR-145 directly suppresses ABCB1 expression by binding to the 3'-UTR of ABCB1 mRNA. SMAD4 siRNA knockdown; HOTAIR siRNA knockdown; EZH2 siRNA knockdown; miR-145 functional assays; 3'-UTR luciferase reporter assay (implied); Western blot; qPCR Biopharmaceutics & drug disposition Medium 30698830
2013 Methadone is an inhibitor (not substrate) of wild-type human P-gp via non-competitive kinetics (IC50 ~2.17 µM), and also stimulates P-gp ATPase activity. Variant P-gp (1236T-2677T-3435T and 1236T-2677A-3435T haplotypes) show reduced inhibition potency and uncompetitive kinetics, demonstrating that ABCB1 haplotype variants alter the mechanism of P-gp/drug interaction. Stable transfection of Flp-In-293 cells with various P-gp genotypes; rhodamine 123 efflux assay; calcein-AM uptake assay; ATPase assay; kinetic analysis PloS one Medium 23527191
2016 P-gp (ABCB1) activity in primary CD4+ T cells reduces intracellular accumulation of raltegravir: CD4+P-gphigh cells accumulated 38.4% less raltegravir than P-gplow cells, and this was reversed by P-gp inhibitor XR9051. In vitro HIV-1 infection increased P-gp mRNA and activity in CD4+ T cells, and P-gphigh CD4+ T cells sustained higher HIV-1 replication. HIV-1 viral load positively correlated with P-gp activity in memory CD4+ T cell subsets. [3H]raltegravir accumulation assay; calcein-AM efflux assay; P-gp inhibitor XR9051 pharmacological blockade; flow cytometry; qRT-PCR; primary CD4+ T cells from HIV-infected patients The Journal of antimicrobial chemotherapy Medium 27334660
2019 Human P-gp (ABCB1) can be purified at large scale from High-Five insect cells using baculovirus expression; the purified protein, when reconstituted into proteoliposomes and nanodiscs, exhibits basal and substrate/inhibitor-modulated ATPase activity, confirming the reconstituted protein is functionally active. An E556Q/E1201Q Walker B mutant defective in ATP hydrolysis was also purified, enabling mechanistic studies. Baculovirus expression in insect cells; IMAC and SEC purification; reconstitution into proteoliposomes and nanodiscs; ATPase activity assay; Walker B mutagenesis Protein expression and purification High 30851394
2001 Expression of P-glycoprotein (P-170/ABCB1) in CEM lymphoblastoid cells sensitizes them to mitochondria-mediated apoptosis. TNF-alpha and staurosporine (mitochondrion-mediated proapoptotic stimuli) were more effective at inducing cell death in P-170-expressing VBL100 cells than in wild-type cells, associated with mitochondrial membrane hyperpolarization in VBL100 cells under steady-state conditions. In contrast, Fas/CD95 and etoposide-induced apoptosis occurred preferentially in wild-type cells, indicating P-gp expression shifts the apoptotic pathway from plasma membrane-associated (Type I) to mitochondria-associated (Type II) cell death. Comparison of P-170-expressing VBL100 vs wild-type CEM cells; apoptosis assays with TNF-alpha, staurosporine, Fas/CD95, etoposide; mitochondrial membrane potential measurements The Biochemical journal Medium 11311119

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Three decades of P-gp inhibitors: skimming through several generations and scaffolds. Current medicinal chemistry 419 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 353 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 169 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 ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics 146 19165709
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
2018 The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM. Brain, behavior, and immunity 117 30041013
2015 Molecular basis of the polyspecificity of P-glycoprotein (ABCB1): recent biochemical and structural studies. Advances in cancer research 113 25640267
2008 Genuine functions of P-glycoprotein (ABCB1). Current drug metabolism 111 18288958
1996 Age-dependent expression of P-glycoprotein gp170 in Caco-2 cell monolayers. Pharmaceutical research 111 8792427
2007 ABCB1 pharmacogenetics: progress, pitfalls, and promise. Clinical pharmacology and therapeutics 105 17259950
2018 An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus. Expert opinion on drug metabolism & toxicology 96 30010462
2007 Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes. Drug metabolism and disposition: the biological fate of chemicals 85 17954525
2007 Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats. Journal of pharmaceutical sciences 83 17593551
2009 Recent advances in the development of P-gp inhibitors. Anti-cancer agents in medicinal chemistry 82 19442042
2009 P-glycoprotein (P-gp/Abcb1), Abcc2, and Abcc3 determine the pharmacokinetics of etoposide. Clinical cancer research : an official journal of the American Association for Cancer Research 77 20028753
2013 Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib, and dasatinib. Clinical pharmacology and therapeutics 74 24107928
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
2004 Expression of P-glycoprotein (ABCB1) and Mrp1 (ABCC1) in adult rat brain: focus on astrocytes. Brain research 70 15328029
2009 Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma. BMC urology 69 19552816
2006 MDR1/P-glycoprotein (ABCB1) as target for RNA interference-mediated reversal of multidrug resistance. Current drug targets 68 16842213
2023 Genetics of ABCB1 in Cancer. Cancers 66 37686513
2015 Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter. Oncotarget 63 25915534
2007 Genomics and the mechanism of P-glycoprotein (ABCB1). Journal of bioenergetics and biomembranes 62 18058211
2009 Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp. International journal of pharmaceutics 61 19465099
2005 Expression and function of ABCB1 and ABCG2 in human placental tissue. Drug metabolism and disposition: the biological fate of chemicals 60 15640379
2013 Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines. PeerJ 55 24058883
2019 Tepotinib reverses ABCB1-mediated multidrug resistance in cancer cells. Biochemical pharmacology 54 31078601
2022 CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells. Molecular cancer 50 35459184
2017 P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer's Disease. Oxidative medicine and cellular longevity 50 29317984
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
2016 Ferulic acid reverses ABCB1-mediated paclitaxel resistance in MDR cell lines. European journal of pharmacology 48 27262378
2023 Gut microbiome modulates tacrolimus pharmacokinetics through the transcriptional regulation of ABCB1. Microbiome 47 37408070
2020 Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies. International journal of molecular sciences 45 32517082
2012 Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicology and applied pharmacology 45 22464980
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
2020 ABCB1/MDR1/P-gp employs an ATP-dependent twist-and-squeeze mechanism to export hydrophobic drugs. FEBS letters 42 33275773
2017 PXR mediated induction of CYP3A4, CYP1A2, and P-gp by Mitragyna speciosa and its alkaloids. Phytotherapy research : PTR 42 29071751
2019 Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. Journal of psychopharmacology (Oxford, England) 41 30789308
2019 ABCB1 protects bat cells from DNA damage induced by genotoxic compounds. Nature communications 41 31249297
2013 ABCB1 gene polymorphisms, ABCB1 haplotypes and ABCG2 c.421c > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics. Die Pharmazie 41 23469685
2021 Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers. Bioscience reports 40 33543229
2019 Drug-Drug Interactions of P-gp Substrates Unrelated to CYP Metabolism. Current drug metabolism 40 30280663
2018 P-Glycoprotein (P-gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre-eclamptic placenta. Journal of cellular and molecular medicine 40 30256530
2015 Lipid regulation of the ABCB1 and ABCG2 multidrug transporters. Advances in cancer research 38 25640268
2008 Canine ABCB1 and macrocyclic lactones: heartworm prevention and pharmacogenetics. Veterinary parasitology 38 18922637
2016 An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure. The pharmacogenomics journal 37 27897269
2006 Effects of capsaicin on P-gp function and expression in Caco-2 cells. Biochemical pharmacology 37 16674925
2017 Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo. Experimental & molecular medicine 36 28303028
2016 ABCB1 genotyping in the treatment of depression. Pharmacogenomics 36 27918249
2013 Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone. PloS one 36 23527191
2016 ABCB1 and ABCC11 confer resistance to eribulin in breast cancer cell lines. Oncotarget 34 27588398
2009 Dietary regulation of P-gp function and expression. Expert opinion on drug metabolism & toxicology 33 19545213
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
2011 P-glycoprotein (ABCB1) expression in human skin is mainly restricted to dermal components. Experimental dermatology 31 21366702
2015 Revealing the fate of cell surface human P-glycoprotein (ABCB1): The lysosomal degradation pathway. Biochimica et biophysica acta 30 26057472
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
2010 Emerging new technologies in Pharmacogenomics: rapid SNP detection, molecular dynamic simulation, and QSAR analysis methods to validate clinically important genetic variants of human ABC Transporter ABCB1 (P-gp/MDR1). Pharmacology & therapeutics 29 20138191
2007 The P-glycoprotein (ABCB1) linker domain encodes high-affinity binding sequences to alpha- and beta-tubulins. Biochemistry 29 17530867
2020 Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance. Frontiers in pharmacology 28 32903706
2019 ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population. Disease markers 28 31871496
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
2022 USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1. Cells 27 36291159
2017 P-gp/ABCB1 exerts differential impacts on brain and fetal exposure to norbuprenorphine. Pharmacological research 26 28111265
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
2003 Potential roles of P-gp and calcium channels in loperamide and diphenoxylate transport. Toxicology and applied pharmacology 26 14613723
2021 Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer. PloS one 25 34347777
2015 Identification of a nonsense mutation in feline ABCB1. Journal of veterinary pharmacology and therapeutics 25 25660379
2014 Cargoing P-gp inhibitors via nanoparticle sensitizes tumor cells against doxorubicin. International journal of pharmaceutics 25 25437111
2022 Recent Advances on P-Glycoprotein (ABCB1) Transporter Modelling with In Silico Methods. International journal of molecular sciences 23 36499131
2014 Impact of common ABCB1 polymorphism on pharmacokinetics and pharmacodynamics of clopidogrel and its metabolites. Journal of clinical pharmacy and therapeutics 23 25430046
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
2020 Reversal of ABCB1-related multidrug resistance by ERK5-IN-1. Journal of experimental & clinical cancer research : CR 22 32164732
2017 ABCB1 genetic variants in leukemias: current insights into treatment outcomes. Pharmacogenomics and personalized medicine 22 28546766
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
2016 P-glycoprotein (ABCB1) activity decreases raltegravir disposition in primary CD4+P-gphigh cells and correlates with HIV-1 viral load. The Journal of antimicrobial chemotherapy 21 27334660
2019 Large-scale purification of functional human P-glycoprotein (ABCB1). Protein expression and purification 20 30851394
2015 Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 20 25976226
2011 Is there evidence to claim or deny association between variants of the multidrug resistance gene (MDR1 or ABCB1) and inflammatory bowel disease? Inflammatory bowel diseases 20 21887726
2019 CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression. Cell structure and function 19 30760665
2011 BPR1K653, a novel Aurora kinase inhibitor, exhibits potent anti-proliferative activity in MDR1 (P-gp170)-mediated multidrug-resistant cancer cells. PloS one 18 21887256
2010 ABCB1 and ABCG2 expression in the placenta and fetus: an interspecies comparison. Expert opinion on drug metabolism & toxicology 18 20738225

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