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characterized activity profile of CAR and compared with hCAR (show CXADR Antibodies) and mCAR (show CXADR Antibodies); related this to structural homology among the 3 orthologues; 5 alternative splice variants identified and sequenced each of which generated a truncated protein product
The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxralpha (show NR1H4 Antibodies)-/- males fed Bile acids (BAs)-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity.
FXR (show NR1H4 Antibodies) signaling is a bile acid nuclear receptor that regulates lipids and glucose homeostasis and lack of it causes hepatomegaly and liver dysfunction.
These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.
Activation of constitutive androstane receptor results in maintained biliary excretion of bile acids despite a marked decrease of bile acids in liver.
Activation of the nuclear receptor constitutive androstane receptor (CAR) induced FNDC5 (show FNDC5 Antibodies) mRNA expression in the liver.
CAR is important for hepatic clearance of several widely prescribed drugs metabolized by P450 (show POR Antibodies) enzymes, however the fasting-induced (show C10orf10 Antibodies) alterations in P450 (show POR Antibodies)-mediated drug clearance are largely independent of CAR.
The present study has revealed known and novel, as well as common and unique targets of PXR (show NR1I2 Antibodies) and CAR in mouse liver following pharmacological activation using their prototypical ligands.
Results show that circadian disruption activates CAR via sympathetic dysfunction and cholestasis. The nuclear receptor CAR drives NAFLD (show TSC2 Antibodies) to NASH (show SAMSN1 Antibodies), fibrosis, and hepatocellular carcinoma progression
data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin (show INS Antibodies) resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required.
Combining CAR activation with limited beta-catenin (show CTNNB1 Antibodies) activation induces tumorigenesis, and the tumours share a conserved gene expression signature with beta-catenin (show CTNNB1 Antibodies)-positive human hepatocellular carcinoma.
Results suggest that TRIM24 (show TRIM24 Antibodies) is a novel coactivator of the CAR that is involved in cell- and/or promoter- selective transactivation.
An overview of NR1I2 (show NR1I2 Antibodies) and NR1I3 pharmacogenetic studies in various therapeutic fields.
replication confirmed at genome-wide significance the association of loci at FOXE1 with hypothyroidism, and PDE8B, CAPZB and PDE10A with serum TSH. A total of 12 SNPs seemed to explain nearly 7% of the serum TSH variation
Dual ligands of CAR/PXR (show NR1I2 Antibodies) show distinct gene regulation patterns by regulating cross-talk between CAR and PXR (show NR1I2 Antibodies).
Data suggest both PXR (show NR1I2 Antibodies) and CAR are expressed in testis (show XKR3 Antibodies)/Sertoli cells; exposure of Sertoli cells (in vitro model of blood-testis barrier) to PXR (show NR1I2 Antibodies) or CAR ligands (including antiretroviral drugs) up-regulates expression of Pgp/ABCB1 (show ABCB4 Antibodies), BCRP, and MRP4 (show ABCC4 Antibodies). (PXR (show NR1I2 Antibodies) = pregnane X receptor (show NR1I2 Antibodies); CAR = constitutive androstane receptor; Pgp/ABCB1 (show ABCB4 Antibodies) = P-glycoprotein ABCB1 (show ABCB1 Antibodies); BCRP = breast cancer resistance protein; MRP4 (show ABCC4 Antibodies) =multidrug resistance protein 4)
Genome-wide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR (show NR1I2 Antibodies) and PPARalpha (show PPARA Antibodies) in primary human hepatocytes has been presented.
Integrative analysis of four RNA-Seq datasets and differential expression revealed for the first time, splicing alterations of SLC39A14 (show SLC39A14 Antibodies) and NR1I3 in hepatocellular carcinoma.
These results reveal both novel and known targets of hCAR (show CXADR Antibodies) and support the role of hCAR (show CXADR Antibodies) in maintaining the homeostasis of metabolism and cell proliferation in the liver.
Around 42.5% of the overall interindividual variability in warfarin dose requirements was explained : VKORC1 (show VKORC1 Antibodies) genotype accounted for 29.6%, CYP2C9 (show CYP2C9 Antibodies) genotype for 4.3%, age for 3.6%, the CYP4F2 (show CYP4F2 Antibodies) genotype for 3.3%, and CAR/HNF4alpha (show HNF4A Antibodies) (rs2501873/rs3212198) for 1.7%
It is suggested that the functions of PXR (show NR1I2 Antibodies), CAR and AhR (show AHR Antibodies) may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipidemia, atherogenesis, and hypertension.
This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. Multiple transcript variants encoding different isoforms have been found for this gene.
constitutive androstane receptor
, constitutively transactivates RAREs
, nuclear receptor subfamily 1 group I member 3
, orphan nuclear receptor MB67
, constitutive androstane receptor NR1I3
, nuclear receptor constitutive active receptor
, strain Fischer nuclear receptor (CAR)
, constitutive activator of retinoid response
, constitutive active receptor
, constitutive active response
, constitutive androstane nuclear receptor variant 2
, constitutive androstane nuclear receptor variant 3
, constitutive androstane nuclear receptor variant 4
, constitutive androstane nuclear receptor variant 5
, orphan nuclear hormone receptor
, xenobiotic receptor