• Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1-a factor perturbed in the majority of human cancers. (gla.ac.uk)
  • Cloning and mRNA expression analysis of an ABCG2 (BCRP) efflux transporter in rainbow trout (Oncorhynchus mykiss) liver and primary hepatocytes. (irb.hr)
  • The common polymorphisms of the gene ABCG2 coding the efflux transporter BCRP and the gene SLCO1B1 coding the influx transporter OATP1B1 are associated with the interindividual variation in the effectiveness and tolerability of the cholesterol-lowering statins. (helsinki.fi)
  • In conclusion, the efflux transporter BCRP seems to have a greater significance on regulating the concentration of rosuvastatin in the liver than the influx transporter OATP1B1. (helsinki.fi)
  • A number of mechanisms involved in the occurrence of MDR have been described, including the overexpression of one or more ATP binding cassette (ABC) transporter proteins that mediate the efflux of many clinically relevant drugs. (spandidos-publications.com)
  • [ 6 ] while another urate transporter (UAT) has been found to facilitate urate efflux out of the cells. (medscape.com)
  • Key drug efflux transporters operational in preserving the BBB are the P-glycoprotein (Pgp) transporter, which belongs to the ATP-binding cassette (ABC) transporter family, and the breast cancer resistance protein (BCRP) ABCG2 ( 4 , 5 ). (jcancer.org)
  • erdafitinib will increase the level or effect of doxorubicin by P-glycoprotein (MDR1) efflux transporter. (medscape.com)
  • indinavir will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. (medscape.com)
  • abcg2) in apixaban disposition was evaluated in experiments using transporter inhibitors and transporter knockout (KO) rats. (aspetjournals.org)
  • Breast cancer resistance protein, encoded by ABCG2, is known to be an efflux transporter of apixaban and rivaroxaban among DOACs. (ewha.ac.kr)
  • The primary regulators of this "placental barrier" are efflux proteins including the ATP-binding cassette transporter breast cancer resistance protein (human ABCG2/BCRP and rodent Abcg2/Bcrp). (rutgers.edu)
  • 12. Kalalinia F, Elahian F, Hassani M, Kasaeeian J, Behravan J. Phorbol ester TPA modulates chemoresistance in the drug sensitive breast cancer cell line MCF-7 by inducing expression of drug efflux transporter ABCG2. (ac.ir)
  • 13. Kalalinia F, Elahian F, Mosaffa F, Behravan J. Celecoxib up regulates the expression of drug efflux transporter ABCG2 in breast cancer cell lines. (ac.ir)
  • The breast cancer resistance protein (BCRP/ABCG2), an efflux transporter highly expressed on syncytiotrophoblasts, plays a critical role in restricting the placental accumulation of chemicals. (grantome.com)
  • we therefore investigated the replacement of a phenyl ring in baicalein by a meta-carborane to improve its affinity towards the human ABCG2 efflux transporter. (qxmd.com)
  • BCRP is likely to be the dominant transport mechanism for ciprofloxacin efflux in both rat and human jejunum. (ncl.ac.uk)
  • Our work demonstrated that exposure of these cells to valproic acid (VPA) induced mRNA, protein, and functional activity of breast cancer resistance protein (BCRP/ABCG2). (manipal.edu)
  • Because mitoxantrone (MTX) is a strong BCRP substrate and is often used in the treatment of leukemia, we investigated the effect of 24 h proadifen pre-treatment on the cytotoxicity of MTX in leukemic cell lines that are sensitive to MTX (HL-60) and MTX-resistant ABCG2-overexpressing subclone (cBCRP). (spandidos-publications.com)
  • More than 40 ABC transporters have been identified so far, but just a few play a role in MDR, including the breast cancer resistance protein (BCRP/ABCG2). (spandidos-publications.com)
  • Because MTX is a preferential and strong substrate of BCRP, MTX-sensitive HL-60 cell line and an MTX-resistant ABCG2-overexpressing subclone (here referred to as cBCRP) were chosen as the experimental models. (spandidos-publications.com)
  • The level of the SN38 efflux transpoter, ABCG2/BCRP, was investigated in the presence or absence of SCO-101. (scandiononcology.com)
  • Additionally, various flux assays were applied to investigate the effect of SCO-101 on ABCG2/BCRP activity. (scandiononcology.com)
  • Flux assays with ABCG2 /BCRP substrates clearly demonstrated that SCO-101 inhibited the activity of ABCG2 and protein analysis further demonstrated that SCO-101 causes degradation of ABCG2/BCRP. (scandiononcology.com)
  • These preclinical studies demonstrate that SCO-101 sensitizes SN38-resistant colon cancer cells to SN38 through two different mechanisms of actions e.g. inhibition of the SRPK1 kinase and degradation of the ABCG2/BCRP drug efflux pump. (scandiononcology.com)
  • There is also considerable interindividual variation in placental BCRP expression and activity due in large part to a nonsynonymous polymorphism in ABCG2 (421C/A, Q141K) present in 3%-32% of the population depending upon race and ethnicity. (rutgers.edu)
  • To characterize factors affecting milciclib pharmacokinetics, we investigated whether milciclib is a substrate of the multidrug effluX and uptake trans- porters ABCB1 (P-gp), ABCG2 (BCRP), and OATP1A/1B, and the drug-metabolizing enzyme CYP3A, using genetically-modified mouse models and Madin-Darby Canine Kidney (MDCK-II) cells. (srcinhibitors.com)
  • Among the main mechanisms of this multidrug resistance is the overexpression of ATP-binding cassette (ABC) transporters that mediate drug efflux, and, specifically, ABCB1, ABCG2 and ABCC1 are known to cause cancer chemoresistance. (nature.com)
  • In this Review, we highlight the progress achieved in the past 5 years on the three transporters, ABCB1, ABCG2 and ABCC1, that are known to be of clinical importance. (nature.com)
  • Furthermore, genetic modification of ABC transporters by CRISPR-Cas9 and approaches to re-engineer amino acid sequences to change the direction of transport from efflux to import are briefly discussed. (nature.com)
  • mainly involved in uptake, and ABC transporters (ABCs), mainly involved in efflux (e.g. (biorxiv.org)
  • Gene expression analysis of the ABC efflux transporters in rainbow trout (Oncorhynchus mykiss). (irb.hr)
  • Cloning and molecular characterization of apical efflux transporters (ABCB1, ABCB11 and ABCC2) in rainbow trout (Oncorhynchus mykiss) hepatocytes. (irb.hr)
  • Detection and functional characterization of Pgp1 (ABCB1) and MRP3 (ABCC3) efflux transporters in the PLHC-1 fish hepatoma cell line. (irb.hr)
  • Several compounds have been shown to inhibit the efflux activity of ABC transporters, thereby increasing intracellular drug accumulation and sensitising cancer cells to therapy. (spandidos-publications.com)
  • Multiple transporters participate in this process, but mainly ABCG2 and SLC2A9. (medscape.com)
  • The exact biological mechanism(s) by which the BBB limits drug exposure is not clear, but in addition to epithelial tight junctions, enhanced efflux of chemotherapeutic agents out of the CNS space by endothelial cell membrane transporters in brain blood vessels plays a primary role ( 2 ). (jcancer.org)
  • These data demonstrate that apixaban undergoes IE, EER, and RTR that are facilitated by efflux transporters. (aspetjournals.org)
  • Our finding provides a clue into a novel treatment strategy: a combination of ulixertinib with anticancer drugs to attenuate MDR mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters. (cp-456773inhibitor.com)
  • Association between ABCG2, ABCB1, ABCC2 efflux transporters SNP's and irinotecan adverse effects in colorectal cancer patients: a real life study. (cdc.gov)
  • Moreover, there was no difference between influx and efflux amount of TQ in cells with inhibited and non-inhibited MDR1 transporters. (ac.ir)
  • The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2, play a key role in mediating MDR by pumping anticancer drugs out from cancer cells. (oncotarget.com)
  • Ceritinib significantly increased the intracellular accumulation of chemotherapeutic agents such as doxorubicin (DOX) by inhibiting ABCB1 or ABCG2-mediated drug efflux in the transporters-overexpressing cells. (oncotarget.com)
  • Mechanistically, ceritinib is likely a competitive inhibitor of ABCB1 and ABCG2 because it competed with [ 125 I]-iodoarylazidoprazosin for photo affinity labeling of the transporters. (oncotarget.com)
  • On the other hand, at the transporters-inhibiting concentrations, ceritinib did not alter the expression level of ABCB1 and ABCG2, and phosphorylation status of AKT and ERK1/2. (oncotarget.com)
  • Ulixertinib (BVD-523) antagonizes ABCB1- and ABCG2-mediated chemotherapeutic drug resistance. (cp-456773inhibitor.com)
  • Mechanistic investigations revealed that ulixertinib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner, and the in silico docking study predicted that ulixertinib could interact with the substrate-binding sites of both ABCB1 and ABCG2. (cp-456773inhibitor.com)
  • Milciclib showed good brain penetration even in wild-type mice (brain-to-plasma ratio of 1.2), but this was further increased by 5.2-fold when both Abcb1 and Abcg2 were ablated, and to a lesser extent in single Abcb1- or Abcg2-deficient mice. (srcinhibitors.com)
  • Thus, ABCB1 and ABCG2 cooperatively limit milciclib brain penetration. (srcinhibitors.com)
  • Level of resistance to anti-tumor remedies can be a characteristic of tumor and CSCs and triggered by up-regulation of genetics accountable for medication efflux and DNA restoration[4]. (researchhunt.com)
  • Reflection of the medication efflux pump ABCG2 is normally another system of cells to gain healing level of resistance and also an set up CSC gun[46]. (researchhunt.com)
  • Fig. 1: Selected substrates transported by ABCB1, ABCG2 and ABCC1. (nature.com)
  • This study aimed to investigate the association between gene variants and bleeding complications during treatment with ABCG2 substrates (apixaban and rivaroxaban). (ewha.ac.kr)
  • We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. (gla.ac.uk)
  • However, these drugs have little effect on brain metastasis due to the combined effects of poor penetration of the blood-brain barrier and their removal from the central nervous system (CNS) by the p-glycoprotein (Pgp) drug efflux pump. (jcancer.org)
  • In vitro, milciclib was transported by mAbcg2, and this was inhibited by the ABCG2 inhibitor Ko143. (srcinhibitors.com)
  • Here, we found that ceritinib remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo . (oncotarget.com)
  • One mechanism that reduces placental accumulation of environmental chemicals is active transport by efflux proteins. (grantome.com)
  • The results showed that ulixertinib, at non-toxic concentrations, significantly reversed ATP-binding cassette subfamily B member 1 (ABCB1)- and ATP-binding cassette subfamily G member 2 (ABCG2)-mediated MDR. (cp-456773inhibitor.com)
  • Conclusion: The modified HAS-BLED score, a history of bleeding, concurrent use of PPI, ABCG2 rs3114018, and ABCB1 rs1045642 were significantly associated with the risk of bleeding complications in patients on apixaban and rivaroxaban, after adjusting for other confounders. (ewha.ac.kr)
  • E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. (gla.ac.uk)
  • The cytotoxic activity of OTS964 was limited in B1/G2 cells relative to that in parental PEL cells, and that this effect can be partially re-sensitized by a known inhibitor of ABCB1 or ABCG2. (biomedcentral.com)
  • Flow cytometry was employed to analyze the accumulation or efflux of chemotherapy drugs. (bvsalud.org)
  • Furthermore, the E2F1-ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. (gla.ac.uk)
  • Limbal epithelial sheets with 5% human AB serum showed the greatest increase in ABCG2 efflux activity (JC1 low ), p63α expression, and CFE compared in both conditions without HAM and with HAM, respectively. (elsevierpure.com)
  • ABCG2 efflux activity, p63α and CK15 expressions, and CFE were also increased in limbal epithelial sheets on HAMS as well. (elsevierpure.com)
  • Western blot analysis and immunofluorescence experiments showed that PPI reduced the expression of GRP78, E-cadherin, N-cadherin, Vimentin, and ABCG2 in SR-HCC cells. (bvsalud.org)
  • overexpressing cells, ulixertinib antagonized MDR by attenuating the efflux function of ABCB1. (cp-456773inhibitor.com)
  • Similarly, in ABCG2-overexpressing cells, ulixertinib inhibited the efflux activity of ABCG2 and reversed resistance to substrate anticancer drugs. (cp-456773inhibitor.com)
  • In BTC, ABCG2 was proven to end up being over-expressed in BTC growth spheres and in Compact disc44+/Compact disc133+ cells, producing it a applicant for medicinal involvement in putative BTC CSCs[43,47,48]. (researchhunt.com)
  • Hematoxylin and eosin (HE) staining of tumor tissue specimens, along with immunohistochemistry (IHC), were conducted to evaluate the expression levels of Ki67, GRP78, N-cadherin, Vimentin, and ABCG2. (bvsalud.org)
  • Outcomes evaluated were outgrowth sheet size from limbal explants, expression of stem/progenitor cell markers p63α, ABCG2 and CK15, and colony formation efficiency (CFE). (elsevierpure.com)
  • Findings from chromatin immunoprecipitation and luciferase assays showed that VPA enhances the binding of PPARa to its response element in the ABCG2 promoter, resulting in elevated ABCG2 transcriptional activity. (manipal.edu)
  • Human promyelocytic leukemia cell line HL-60 was purchased from the American Type Culture Collection (ATCC, Rockville, MD, USA) and its ABCG2-overexpressing subclone (here referred to as cBCRP) was kindly provided by Dr Balazs Sarkadi (Membrane Research Group, Hungarian Academy of Sciences, Budapest, Hungary) ( 10 ). (spandidos-publications.com)
  • also known as ABCG2), and causes a poor 5-year survival rate of human patients. (qxmd.com)
  • Upon oral administration of milciclib, its plasma exposure in Abcb1a/1b-/-, Abcg2-/-, and Abcb1a/1b;Abcg2-/- mice was similar to that found in wild-type mice. (srcinhibitors.com)
  • Five single nucleotide polymorphisms (SNPs) of ABCG2 were selected. (ewha.ac.kr)
  • The reversal effects of ulixertinib were not related to the down-regulation or change of subcellular localization of ABCB1 or ABCG2. (cp-456773inhibitor.com)
  • In the intestines, the ABCG2 protein helps release (secrete) a substance called urate into the urine. (medlineplus.gov)
  • The ABCG2 protein also transports certain drugs out of cells. (medlineplus.gov)
  • Another variant creates a premature stop signal in the instructions for making the ABCG2 protein (written as Gln126Ter or Q126X), which results in no functional ABCG2 protein. (medlineplus.gov)
  • Histone deacetylase inhibitors (HDIs) induced not only relocalization to cell surface, but also restored protein expression to levels similar to the wild-type, coupled with increased ABCG2 specific efflux. (nih.gov)
  • In another way, HDI-induced ABCG2 Q141K rescue occurred at multiple levels by modulating the protein transcription, folding and trafficking. (nih.gov)
  • Ceefourin 1 is a selective MRP (multidrug resistance-associated protein) 4 inhibitor (IC 50 = 2.6 μ M). Selective for MRP4 over P-gp, MRP1 and ABCG2. (tocris.com)
  • P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. (amsterdamumc.org)
  • Concerning the R123, regardless if a particular site is actually proposed to thrive around the dimer interface (in terms of mitoxantrone) in the wild-style of necessary protein, our research with all the recently reported cholesterol localization about individual ABCG2 crystal design shows that it location manage alternatively be area of the translocation path (Fig. 12B, yellow dashed range). (premier1888.com)
  • 6. Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. (nih.gov)
  • 13. Enhancing chemosensitivity in ABCB1- and ABCG2-overexpressing cells and cancer stem-like cells by an Aurora kinase inhibitor CCT129202. (nih.gov)
  • 17. Vatalanib sensitizes ABCB1 and ABCG2-overexpressing multidrug resistant colon cancer cells to chemotherapy under hypoxia. (nih.gov)
  • 2020 ) Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model. (neurotree.org)
  • ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis. (cdc.gov)
  • 10. ABCG2-meditated multidrug resistance and tumor-initiating capacity of side population cells from colon cancer. (nih.gov)
  • 8 Biochanin A and formononetin may also reduce and possibly reverse multi-drug resistance by inhibiting P-glycoprotein-mediated efflux, suggesting they could potentially increase the absorption/bioavailability of coadministered drugs that are P-gp substrates. (donnieyance.com)
  • Genetic changes in the ABCG2 gene are associated with a condition called gout, which is a form of arthritis that causes painful joint inflammation. (medlineplus.gov)
  • ABCG2 gene changes associated with gout decrease the protein's ability to release urate. (medlineplus.gov)
  • Variants in the ABCG2 gene reduce the removal of urate from the blood, which causes the blood level of urate to rise. (medlineplus.gov)
  • While changes in the ABCG2 gene can alter urate levels in the body, they are not enough to cause gout by themselves. (medlineplus.gov)
  • 2. Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. (nih.gov)
  • Recently, the Q141K polymorphism in ABCG2 gene was associated with elevated serum urate levels and gout. (nih.gov)
  • Impact of ABCG2 Gene Polymorphism on the Predisposition to Psoriasis. (cdc.gov)
  • Here, the interaction between uremic toxins and two important efflux pumps, viz. (rug.nl)
  • In addition, clinically relevant genetic polymorphisms of ABCG2 have been shown to impact on the pharmacokinetics (e.g., irinotecan 6 , rosuvastatin 7,8 , atorvastatin 8 , sulfasalasine 9 and topotecan 10 ) and toxicity (e.g., gefitinib-induced diarrhoea 11 ) of marketed drugs. (cyprotex.com)
  • The polymorphism impairs the normal expression, localization and function of ABCG2. (nih.gov)
  • We have studied the biology underlying altered expression and localization of ABCG2 Q141K, and screened compounds for their ability to restore proper function and localization of the variant. (nih.gov)
  • 8. ABCG2: the key to chemoresistance in cancer stem cells? (nih.gov)
  • This experimental system will serve in further elucidating the physiological consequences of Abcg2 mediated changes in ceramide levels on stem cells in vivo. (uni-frankfurt.de)
  • 15. Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. (nih.gov)
  • Ceefourin 1 inhibits cAMP efflux from acute myeloid leukemia cells (AML) and promotes apoptosis in combination with Histamine (Cat. (tocris.com)
  • We propose that Abcg2 and ceramide interact and that this interaction leads to changes in the absolute or relative amounts of ceramide. (uni-frankfurt.de)
  • And also this signifies that ABCG2 has a high reliance with the biophysical characteristics of your own membrane. (premier1888.com)
  • Considered one of the basic challenges is only constrained in formation is obtainable about the creation of an artificial niche to keep implanted stem progenitor cells in an en vironment keeping competence for regeneration. (agckinase.com)
  • partial areas of 0.563 and 0.396 nm 2 for DMPC and cholesterol respectively), it was found that the presence of ABCG2 increases the A L up to values similar to pure DMPC membranes (0.591 nm 2 ), corresponding to a 10% increase on the membrane's mean areas per lipid (partial areas of 0.661 and 0.316 nm 2 for DMPC and cholesterol, respectively). (premier1888.com)
  • Therefore, these data show a stronger effect by ABCG2 in the surrounding lipid environment when compared to P-gp. (premier1888.com)
  • Additionally, we show that active Abcg2 can increase the ceramide concentration in cell culture supernatant. (uni-frankfurt.de)
  • Finally we demonstrate that Abcg2 protects from ceramide induced cytotoxicity in human cell lines. (uni-frankfurt.de)