{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:23:55Z","timestamp":1782483835629,"version":"3.54.5"},"reference-count":170,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China Youth Program","award":["82204748"],"award-info":[{"award-number":["82204748"]}]},{"name":"National Natural Science Foundation of China Youth Program","award":["202423l10050002"],"award-info":[{"award-number":["202423l10050002"]}]},{"name":"National Natural Science Foundation of China Youth Program","award":["Anhui Kesheng Secret [2024] No. 407"],"award-info":[{"award-number":["Anhui Kesheng Secret [2024] No. 407"]}]},{"name":"National Natural Science Foundation of China Youth Program","award":["zyyzdxk-2023095"],"award-info":[{"award-number":["zyyzdxk-2023095"]}]},{"name":"National Natural Science Foundation of China Youth Program","award":["Wan Ren She Mi [2025] No. 11"],"award-info":[{"award-number":["Wan Ren She Mi [2025] No. 11"]}]},{"name":"Key Science &amp; Technology Project of Anhui Province","award":["82204748"],"award-info":[{"award-number":["82204748"]}]},{"name":"Key Science &amp; Technology Project of Anhui Province","award":["202423l10050002"],"award-info":[{"award-number":["202423l10050002"]}]},{"name":"Key Science &amp; Technology Project of Anhui Province","award":["Anhui Kesheng Secret [2024] No. 407"],"award-info":[{"award-number":["Anhui Kesheng Secret [2024] No. 407"]}]},{"name":"Key Science &amp; Technology Project of Anhui Province","award":["zyyzdxk-2023095"],"award-info":[{"award-number":["zyyzdxk-2023095"]}]},{"name":"Key Science &amp; Technology Project of Anhui Province","award":["Wan Ren She Mi [2025] No. 11"],"award-info":[{"award-number":["Wan Ren She Mi [2025] No. 11"]}]},{"name":"Demonstration Project for Science and Technology Specialists in Anhui Province","award":["82204748"],"award-info":[{"award-number":["82204748"]}]},{"name":"Demonstration Project for Science and Technology Specialists in Anhui Province","award":["202423l10050002"],"award-info":[{"award-number":["202423l10050002"]}]},{"name":"Demonstration Project for Science and Technology Specialists in Anhui Province","award":["Anhui Kesheng Secret [2024] No. 407"],"award-info":[{"award-number":["Anhui Kesheng Secret [2024] No. 407"]}]},{"name":"Demonstration Project for Science and Technology Specialists in Anhui Province","award":["zyyzdxk-2023095"],"award-info":[{"award-number":["zyyzdxk-2023095"]}]},{"name":"Demonstration Project for Science and Technology Specialists in Anhui Province","award":["Wan Ren She Mi [2025] No. 11"],"award-info":[{"award-number":["Wan Ren She Mi [2025] No. 11"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project","award":["82204748"],"award-info":[{"award-number":["82204748"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project","award":["202423l10050002"],"award-info":[{"award-number":["202423l10050002"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project","award":["Anhui Kesheng Secret [2024] No. 407"],"award-info":[{"award-number":["Anhui Kesheng Secret [2024] No. 407"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project","award":["zyyzdxk-2023095"],"award-info":[{"award-number":["zyyzdxk-2023095"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project","award":["Wan Ren She Mi [2025] No. 11"],"award-info":[{"award-number":["Wan Ren She Mi [2025] No. 11"]}]},{"name":"2025 Anhui Province Postdoctoral Research Project","award":["82204748"],"award-info":[{"award-number":["82204748"]}]},{"name":"2025 Anhui Province Postdoctoral Research Project","award":["202423l10050002"],"award-info":[{"award-number":["202423l10050002"]}]},{"name":"2025 Anhui Province Postdoctoral Research Project","award":["Anhui Kesheng Secret [2024] No. 407"],"award-info":[{"award-number":["Anhui Kesheng Secret [2024] No. 407"]}]},{"name":"2025 Anhui Province Postdoctoral Research Project","award":["zyyzdxk-2023095"],"award-info":[{"award-number":["zyyzdxk-2023095"]}]},{"name":"2025 Anhui Province Postdoctoral Research Project","award":["Wan Ren She Mi [2025] No. 11"],"award-info":[{"award-number":["Wan Ren She Mi [2025] No. 11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic\u2013intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges.<\/jats:p>","DOI":"10.3390\/ijms26168029","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"8029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Yuanbo","family":"Bi","sequence":"first","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-0635","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-0897","authenticated-orcid":false,"given":"Daiyin","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1042\/EBC20210020","article-title":"Nuclear receptors: From molecular mechanisms to therapeutics","volume":"65","author":"Frigo","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1146\/annurev.biochem.68.1.559","article-title":"Nuclear-receptor ligands and ligand-binding domains","volume":"68","author":"Weatherman","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0092-8674(00)80900-9","article-title":"An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway","volume":"92","author":"Kliewer","year":"1998","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.drudis.2013.01.001","article-title":"3D structures and ligand specificities of nuclear xenobiotic receptors CAR, PXR and VDR","volume":"18","author":"Wu","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.addr.2010.07.002","article-title":"Nuclear receptors as drug targets for metabolic disease","volume":"62","author":"Schulman","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155999","DOI":"10.1016\/j.metabol.2024.155999","article-title":"Global burden of metabolic diseases, 1990\u20132021","volume":"160","author":"Zhang","year":"2024","journal-title":"Metabolism"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.tips.2012.07.003","article-title":"Targeting xenobiotic receptors PXR and CAR for metabolic diseases","volume":"33","author":"Gao","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.jmb.2014.12.022","article-title":"Developing Adnectins that target SRC co-activator binding to PXR: A structural approach toward understanding promiscuity of PXR","volume":"427","author":"Khan","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/j.jmb.2013.04.012","article-title":"Structural and functional analysis of the human nuclear xenobiotic receptor PXR in complex with RXR\u03b1","volume":"425","author":"Wallace","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.2337\/db12-1039","article-title":"PXR ablation alleviates diet-induced and genetic obesity and insulin resistance in mice","volume":"62","author":"He","year":"2013","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1172\/JCI200112876","article-title":"The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression","volume":"108","author":"Nakae","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1476-5381.2010.01129.x","article-title":"Pregnane X receptor-and CYP3A4-humanized mouse models and their applications","volume":"163","author":"Cheng","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2174\/1389200054633844","article-title":"Structure and function of the human nuclear xenobiotic receptor PXR","volume":"6","author":"Carnahan","year":"2005","journal-title":"Curr. Drug Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.mam.2009.04.002","article-title":"Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects","volume":"30","author":"Ascenzi","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s10577-018-9583-2","article-title":"Nuclear localization signal region in nuclear receptor PXR governs the receptor association with mitotic chromatin","volume":"26","author":"Rana","year":"2018","journal-title":"Chromosome Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1126\/science.1060762","article-title":"The human nuclear xenobiotic receptor PXR: Structural determinants of directed promiscuity","volume":"292","author":"Watkins","year":"2001","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0022-2836(03)00795-2","article-title":"Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor","volume":"331","author":"Watkins","year":"2003","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1016\/j.csbj.2022.06.020","article-title":"Discrepancy in interactions and conformational dynamics of pregnane X receptor (PXR) bound to an agonist and a novel competitive antagonist","volume":"20","author":"Rashidian","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8579","DOI":"10.1021\/bi0602821","article-title":"Human PXR forms a tryptophan zipper-mediated homodimer","volume":"45","author":"Noble","year":"2006","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/protein\/gzn017","article-title":"Construction and characterization of a fully active PXR\/SRC-1 tethered protein with increased stability","volume":"21","author":"Wang","year":"2008","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1172\/JCI3703","article-title":"The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions","volume":"102","author":"Lehmann","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1210\/me.2005-0156","article-title":"The nuclear xenobiotic receptor pregnane X receptor: Recent insights and new challenges","volume":"19","author":"Orans","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.bbagrm.2016.02.013","article-title":"Small-molecule modulators of PXR and CAR","volume":"1859","author":"Chai","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Regul. Mech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1124\/dmd.108.022723","article-title":"A double transgenic mouse model expressing human pregnane X receptor and cytochrome P450 3A4","volume":"36","author":"Ma","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.1038\/s41467-024-48472-1","article-title":"Chemical manipulation of an activation\/inhibition switch in the nuclear receptor PXR","volume":"15","author":"Huber","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cell.2014.03.012","article-title":"Nuclear receptors, RXR, and the big bang","volume":"157","author":"Evans","year":"2014","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2016.08.001","article-title":"Drug metabolism in the liver","volume":"21","author":"Almazroo","year":"2017","journal-title":"Clin. Liver Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155271","DOI":"10.1016\/j.phymed.2023.155271","article-title":"Chlorogenic acid regulates the expression of NPC1L1 and HMGCR through PXR and SREBP2 signaling pathways and their interactions with HSP90 to maintain cholesterol homeostasis","volume":"123","author":"Meng","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14146","DOI":"10.1074\/jbc.M212482200","article-title":"A novel distal enhancer module regulated by pregnane X receptor\/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression","volume":"278","author":"Wang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1182\/blood-2003-07-2490","article-title":"Targeting the multidrug resistance-1 transporter in AML: Molecular regulation and therapeutic strategies","volume":"104","author":"Mahadevan","year":"2004","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14581","DOI":"10.1074\/jbc.M010173200","article-title":"Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin","volume":"276","author":"Geick","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1053\/j.gastro.2003.12.046","article-title":"Consequences of bile duct obstruction on intestinal expression and function of multidrug resistance-associated protein 2","volume":"126","author":"Dietrich","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1074\/jbc.M109326200","article-title":"Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor","volume":"277","author":"Kast","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.2337\/dc14-S081","article-title":"Diagnosis and classification of diabetes mellitus","volume":"37","author":"Association","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1210\/endrev\/bnaa023","article-title":"Cellular and molecular mechanisms of metformin action","volume":"42","author":"LaMoia","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1056\/NEJM199508313330902","article-title":"Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus","volume":"333","author":"DeFronzo","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1016\/j.bcp.2011.08.023","article-title":"Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene","volume":"82","author":"Krausova","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejps.2017.02.031","article-title":"Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway","volume":"102","author":"Shan","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1172\/JCI579","article-title":"Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans","volume":"101","author":"Petersen","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E685","DOI":"10.1152\/ajpendo.00253.2003","article-title":"Novel concepts in insulin regulation of hepatic gluconeogenesis","volume":"285","author":"Barthel","year":"2003","journal-title":"Am. J. Physiol. -Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7931","DOI":"10.1128\/MCB.24.18.7931-7940.2004","article-title":"Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes","volume":"24","author":"Kodama","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33705","DOI":"10.1074\/jbc.M101215200","article-title":"Gene-and activation-specific mechanisms for insulin inhibition of basal and glucocorticoid-induced insulin-like growth factor binding protein-1 and phosphoenolpyruvate carboxykinase transcription","volume":"276","author":"Yeagley","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nature01667","article-title":"Insulin-regulated hepatic gluconeogenesis through FOXO1\u2013PGC-1\u03b1 interaction","volume":"423","author":"Puigserver","year":"2003","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1016\/j.apsb.2021.09.031","article-title":"PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4\u03b1\u2013GLUT2 pathway","volume":"12","author":"Liu","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bcp.2018.01.001","article-title":"Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver","volume":"148","author":"Kummu","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1002\/tox.24094","article-title":"Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage","volume":"39","author":"Shan","year":"2024","journal-title":"Environ. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/toxsci\/kfad056","article-title":"Maternal PBDE exposure disrupts gut microbiome and promotes hepatic proinflammatory signaling in humanized PXR-transgenic mouse offspring over time","volume":"194","author":"Kim","year":"2023","journal-title":"Toxicol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"Hu","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","article-title":"Obesity phenotypes, diabetes, and cardiovascular diseases","volume":"126","author":"Tchernof","year":"2020","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.1016\/j.cell.2024.08.012","article-title":"A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense","volume":"187","author":"Zhang","year":"2024","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5919","DOI":"10.1038\/s41467-024-50198-z","article-title":"B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2308771","DOI":"10.1002\/advs.202308771","article-title":"Pregnane X Receptor Activation in Liver Macrophages Protects against Endotoxin-Induced Liver Injury","volume":"11","author":"Zhao","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Okamura, M., Shizu, R., Abe, T., Kodama, S., Hosaka, T., Sasaki, T., and Yoshinari, K. (2020). PXR functionally interacts with NF-\u03baB and AP-1 to downregulate the inflammation-induced expression of chemokine CXCL2 in mice. Cells, 9.","DOI":"10.3390\/cells9102296"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kim, S., Choi, S., Dutta, M., Asubonteng, J.O., Polunas, M., Goedken, M., Gonzalez, F.J., Cui, J.Y., and Gyamfi, M.A. (2021). Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity-and inflammation-prone gut microbiome signature. Biochem. Pharmacol., 193.","DOI":"10.1016\/j.bcp.2021.114698"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gebreyesus, L.H., Choi, S., Neequaye, P., Mahmoud, M., Mahmoud, M., Ofosu-Boateng, M., Twum, E., Nnamani, D.O., Wang, L., and Yadak, N. (2024). Pregnane X receptor knockout mitigates weight gain and hepatic metabolic dysregulation in female C57BL\/6 J mice on a long-term high-fat diet. Biomed. Pharmacother., 173.","DOI":"10.1016\/j.biopha.2024.116341"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/S0140-6736(22)02403-5","article-title":"Contemporary medical, device, and surgical therapies for obesity in adults","volume":"401","author":"Perdomo","year":"2023","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1161\/01.CIR.89.5.2462","article-title":"A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association","volume":"89","author":"Stary","year":"1994","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/cvr\/cvy079","article-title":"PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages","volume":"114","author":"Ding","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"C13","DOI":"10.1016\/j.jacc.2005.10.065","article-title":"Pathology of the vulnerable plaque","volume":"47","author":"Virmani","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41569-018-0110-0","article-title":"Platelet biology and functions: New concepts and clinical perspectives","volume":"16","author":"Heemskerk","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/cvr\/cvy044","article-title":"Non-genomic effects of nuclear receptors: Insights from the anucleate platelet","volume":"114","author":"Unsworth","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Flora, G.D., Sahli, K.A., Sasikumar, P., Holbrook, L.-M., Stainer, A.R., AlOuda, S.K., Crescente, M., Sage, T., Unsworth, A.J., and Gibbins, J.M. (2019). Non-genomic effects of the Pregnane X Receptor negatively regulate platelet functions, thrombosis and haemostasis. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-53218-x"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/cvr\/cvr330","article-title":"Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress","volume":"93","author":"Swales","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"loaf002","DOI":"10.1093\/lifemeta\/loaf002","article-title":"Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite indole-3-propionate","volume":"4","author":"Qi","year":"2025","journal-title":"Life Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1056\/NEJM199511163332002","article-title":"Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population","volume":"333","author":"Miettinen","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1194\/jlr.M800608-JLR200","article-title":"Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in apoE deficient mice","volume":"50","author":"Zhou","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Brown, C., Kariuki, W., Zhong, H.A., Kippes, A., and Sui, Y. (2024). Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1398462"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e000492","DOI":"10.1161\/JAHA.113.000492","article-title":"Bisphenol A increases atherosclerosis in pregnane X receptor-humanized ApoE deficient mice","volume":"3","author":"Sui","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1074\/jbc.M116.767277","article-title":"Heat shock protein 90 modulates lipid homeostasis by regulating the stability and function of sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating protein","volume":"292","author":"Kuan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1007\/s00204-023-03575-4","article-title":"Adverse outcome pathway for pregnane X receptor-induced hypercholesterolemia","volume":"97","author":"Itkonen","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCRESAHA.114.301621","article-title":"PCSK9: A key modulator of cardiovascular health","volume":"114","author":"Seidah","year":"2014","journal-title":"Circ. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/s41467-025-56642-y","article-title":"The hypolipidemic effect of MI-883, the combined CAR agonist\/PXR antagonist, in diet-induced hypercholesterolemia model","volume":"16","author":"Dusek","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wu, G., Wei, X., Li, D., Xiao, G., Jia, C., Zeng, Z., and Chen, Z. (2024). Selection and evaluation of quality markers for the regulation of PXR-CYP3A4\/FXR-LXR\u03b1 by Exocarpium Citri Grandis for the treatment of hyperlipidaemia with dispelling blood stasis and removing phlegm. Biomed. Pharmacother., 170.","DOI":"10.1016\/j.biopha.2023.116089"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.3350\/cmh.2022.0367","article-title":"MAFLD: How is it different from NAFLD?","volume":"29","author":"Gofton","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/0092-8674(94)90252-6","article-title":"Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein","volume":"79","author":"Schaffer","year":"1994","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"156054","DOI":"10.1016\/j.metabol.2024.156054","article-title":"Hepatocyte-specific SLC27A4 deletion ameliorates nonalcoholic fatty liver disease in mice via suppression of phosphatidylcholine-mediated PXR activation","volume":"162","author":"Shen","year":"2025","journal-title":"Metabolism"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"28210","DOI":"10.1074\/jbc.272.45.28210","article-title":"Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPAR\u03b1 and PPAR\u03b3 activators","volume":"272","author":"Martin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Rakhshandehroo, M., Hooiveld, G., M\u00fcller, M., and Kersten, S. (2009). Comparative analysis of gene regulation by the transcription factor PPAR\u03b1 between mouse and human. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006796"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.toxlet.2024.07.003","article-title":"Metabolomics reveals dysregulated all-trans retinoic acid and polyunsaturated fatty acid metabolism contribute to PXR-induced hepatic steatosis in mice","volume":"398","author":"Yan","year":"2024","journal-title":"Toxicol. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Barretto, S.A., Lasserre, F., Fougerat, A., Smith, L., Fougeray, T., Lukowicz, C., Polizzi, A., Smati, S., R\u00e9gnier, M., and Naylies, C. (2019). Gene expression profiling reveals that PXR activation inhibits hepatic PPAR\u03b1 activity and decreases FGF21 secretion in male C57Bl6\/J mice. Int. J. Mol. Sci., 20.","DOI":"10.20944\/preprints201907.0069.v1"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e002548","DOI":"10.1136\/jitc-2021-002548","article-title":"S100A4 enhances protumor macrophage polarization by control of PPAR-\u03b3-dependent induction of fatty acid oxidation","volume":"9","author":"Liu","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1053\/j.gastro.2007.11.037","article-title":"Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPAR\u03b3 in promoting steatosis","volume":"134","author":"Zhou","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kotiya, D., Jaiswal, B., Ghose, S., Kaul, R., Datta, K., and Tyagi, R.K. (2016). Role of PXR in hepatic cancer: Its influences on liver detoxification capacity and cancer progression. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164087"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"30075","DOI":"10.1074\/jbc.M114.578781","article-title":"Xenobiotic pregnane X receptor (PXR) regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells","volume":"289","author":"Wang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature10558","article-title":"Non-canonical inflammasome activation targets caspase-11","volume":"479","author":"Kayagaki","year":"2011","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00204-014-1348-x","article-title":"Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms","volume":"89","author":"Bitter","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/s41568-023-00602-5","article-title":"Cancers make their own luck: Theories of cancer origins","volume":"23","author":"Jassim","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1126\/science.347.6217.12","article-title":"The bad luck of cancer: Analysis suggests most cases can\u2019t be prevented","volume":"347","year":"2015","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41586-021-04224-5","article-title":"Cancer risk across mammals","volume":"601","author":"Vincze","year":"2022","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/eva.12018","article-title":"The real war on cancer: The evolutionary dynamics of cancer suppression","volume":"6","author":"Nunney","year":"2013","journal-title":"Evol. Appl."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"154057","DOI":"10.1016\/j.tox.2025.154057","article-title":"AFB1 consolidates HBV harm to induce liver injury and carcinogenic risk by inactivating FTCD-AS1-PXR-MASP1 axis","volume":"511","author":"Xing","year":"2025","journal-title":"Toxicology"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kostecki, G., Chuang, K., Buxton, A., and Dakshanamurthy, S. (2025). Dose-Dependent PFESA-BP2 Exposure Increases Risk of Liver Toxicity and Hepatocellular Carcinoma. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020098"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Shi, T., Fan, Q.-Y., Liu, S.-B., and Zhang, S.-Y. (2024). Pregnane X receptor (PXR) deficiency promotes hepatocarcinogenesis via induction of Akr1c18 expression and prostaglandin F2\u03b1 (PGF2\u03b1) levels. Biochem. Pharmacol., 225.","DOI":"10.1016\/j.bcp.2024.116309"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0305-7372(84)90037-9","article-title":"Some thoughts on resistance to cancer chemotherapy","volume":"11","author":"Carter","year":"1984","journal-title":"Cancer Treat. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Wang, Z.-J., Zhan, X.-Y., Ma, L.-Y., Yao, K., Dai, H.-Y., Santhanam, R.K., Zhou, M.-S., and Jia, H. (2024). Activation of the \u03b3-secretase\/NICD-PXR\/Notch pathway induces Taxol resistance in triple-negative breast cancer. Biochem. Pharmacol., 230.","DOI":"10.1016\/j.bcp.2024.116577"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41419-022-05537-7","article-title":"TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs","volume":"14","author":"Wang","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"18549","DOI":"10.1021\/acs.jmedchem.4c01926","article-title":"First-in-Class Small Molecule Degrader of Pregnane X Receptor Enhances Chemotherapy Efficacy","volume":"67","author":"Huber","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1016\/j.str.2024.09.016","article-title":"PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network","volume":"32","author":"Huber","year":"2024","journal-title":"Structure"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1016\/j.apsb.2023.07.014","article-title":"The F-box-only protein 44 regulates pregnane X receptor protein level by ubiquitination and degradation","volume":"13","author":"Gee","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.cell.2023.03.003","article-title":"Metastasis","volume":"186","author":"Gerstberger","year":"2023","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nrc.2016.25","article-title":"Targeting metastasis","volume":"16","author":"Steeg","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s12029-021-00801-z","article-title":"EMT and inflammation: Crossroads in HCC","volume":"54","author":"Sengez","year":"2023","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1042\/BCJ20240172","article-title":"Pregnane X receptor inhibits the transdifferentiation of hepatic stellate cells by down-regulating periostin expression","volume":"481","author":"Sato","year":"2024","journal-title":"Biochem. J."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Liu, Y., Qin, J., Li, X., and Wu, G. (2024). Oxysterols in tumor immune microenvironment (TIME). J. Steroid Biochem. Mol. Biol., 245.","DOI":"10.1016\/j.jsbmb.2024.106634"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ccell.2023.12.016","article-title":"A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization","volume":"42","author":"Pacini","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.molpha.2025.100019","article-title":"LIM and SH3 Protein 2 (Lasp2) is a novel PXR target gene in mouse liver","volume":"107","author":"Konzack","year":"2025","journal-title":"Mol. Pharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1002\/mc.22700","article-title":"Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients","volume":"56","author":"Zhang","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15389","DOI":"10.1002\/jcb.28806","article-title":"Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells","volume":"120","author":"Zhang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1476-4598-7-31","article-title":"The LIM and SH3 domain protein family: Structural proteins or signal transducers or both?","volume":"7","author":"Grunewald","year":"2008","journal-title":"Mol. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Li, J., Hu, S., Zhang, Z., Qian, L., Xue, Q., and Qu, X. (2020). LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK\/ERK pathway. Biomed. Pharmacother., 127.","DOI":"10.1016\/j.biopha.2020.110154"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e70185","DOI":"10.1111\/jcmm.70185","article-title":"The combination of FLCWK with 5-FU inhibits colon cancer and multidrug resistance by activating PXR to suppress the IL-6\/STAT3 pathway","volume":"28","author":"Zhong","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/03602532.2024.2366948","article-title":"Advances in drug resistance of osteosarcoma caused by pregnane X receptor","volume":"56","author":"Mao","year":"2024","journal-title":"Drug Metab. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e14120","DOI":"10.1111\/eci.14120","article-title":"Zinc finger proteins and ATP-binding cassette transporter-dependent multidrug resistance","volume":"54","author":"Barzegar","year":"2024","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1073\/pnas.051551698","article-title":"The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity","volume":"98","author":"Staudinger","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7500","DOI":"10.1073\/pnas.130155097","article-title":"St. John\u2019s wort induces hepatic drug metabolism through activation of the pregnane X receptor","volume":"97","author":"Moore","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1210\/mend.14.1.0409","article-title":"The pregnane X receptor: A promiscuous xenobiotic receptor that has diverged during evolution","volume":"14","author":"Jones","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1289\/ehp.6560","article-title":"Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR)","volume":"112","author":"Tabb","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00228-012-1388-1","article-title":"Effect of the CYP3A inhibitor ketoconazole on the PXR-mediated induction of CYP3A activity","volume":"69","author":"Fuchs","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.2174\/1381612827666210715155809","article-title":"The intracellular mechanism of berberine-induced inhibition of CYP3A4 activity","volume":"27","author":"Feng","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mce.2019.02.002","article-title":"Clinical applications of small molecule inhibitors of Pregnane X receptor","volume":"485","author":"Staudinger","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1124\/mol.108.049437","article-title":"Computational discovery of novel low micromolar human pregnane X receptor antagonists","volume":"74","author":"Ekins","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/17425255.2024.2309212","article-title":"Regulation of PXR in drug metabolism: Chemical and structural perspectives","volume":"20","author":"Gee","year":"2024","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Su, H., Liang, H., Tian, J., Zheng, L., Li, H., Yang, X., Yin, S., and Bi, H. (2024). Discovery of PXR agonists from Hypericum japonicum: A class of novel nonaromatic acylphloroglucinol-terpenoid adducts. Bioorganic Chem., 147.","DOI":"10.1016\/j.bioorg.2024.107354"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41467-025-56624-0","article-title":"An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.immuni.2014.06.014","article-title":"Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4","volume":"41","author":"Venkatesh","year":"2014","journal-title":"Immunity"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"100059","DOI":"10.1016\/j.jpet.2024.100059","article-title":"Unlocking the potential: FKK6 as a microbial mimicry-based therapy for chronic inflammation-associated colorectal cancer in a murine model","volume":"392","author":"Li","year":"2025","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Dvo\u0159\u00e1k, Z., Vyhl\u00eddalov\u00e1, B., Pe\u010dinkov\u00e1, P., Li, H., Anzenbacher, P., \u0160pi\u010d\u00e1kov\u00e1, A., Anzenbacherov\u00e1, E., Chow, V., Liu, J., and Krause, H. (2024). In vitro safety signals for potential clinical development of the anti-inflammatory pregnane X receptor agonist FKK6. Bioorganic Chem., 144.","DOI":"10.1016\/j.bioorg.2024.107137"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Lynch, C., Margolis, R., Niebler, J., Travers, J., Sakamuru, S., Zhao, T., Klumpp-Thomas, C., Huang, R., and Xia, M. (2024). Identification of human pregnane X receptor antagonists utilizing a high-throughput screening platform. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1448744"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1124\/mol.107.038398","article-title":"Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites","volume":"72","author":"Ekins","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.tips.2024.10.002","article-title":"Novel antagonists reveal the mechanism of PXR inhibition","volume":"45","author":"Kamaraj","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.addr.2010.08.006","article-title":"Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR","volume":"62","author":"Tolson","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/03602530902843483","article-title":"Polymorphism of human cytochrome P450 enzymes and its clinical impact","volume":"41","author":"Zhou","year":"2009","journal-title":"Drug Metab. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/PL00000897","article-title":"Cytochromes P450 and metabolism of xenobiotics","volume":"58","author":"Anzenbacher","year":"2001","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00216-008-1962-7","article-title":"High-performance liquid chromatography\u2013tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites","volume":"391","author":"Nobilis","year":"2008","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Yao, N., Zeng, C., Zhan, T., He, F., Liu, M., Liu, F., Zhang, H., Xiong, Y., and Xia, C. (2019). Oleanolic acid and ursolic acid induce UGT1A1 expression in HepG2 cells by activating PXR rather than CAR. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01111"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s40262-020-00867-1","article-title":"Effect of P-glycoprotein (P-gp) inducers on exposure of P-gp substrates: Review of clinical drug\u2013drug interaction studies","volume":"59","author":"Elmeliegy","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"17562848231163410","DOI":"10.1177\/17562848231163410","article-title":"Drug-induced liver injury: A comprehensive review","volume":"16","author":"Hosack","year":"2023","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Duintjer Tebbens, J., Azar, M., Friedmann, E., Lanzend\u00f6rfer, M., and P\u00e1vek, P. (2018). Mathematical models in the description of pregnane X receptor (PXR)-regulated cytochrome P450 enzyme induction. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061785"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2174\/138920006776873526","article-title":"Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds","volume":"7","author":"Reschly","year":"2006","journal-title":"Curr. Drug Metab."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Pu, S., Pan, Y., Wang, Z., Liu, H., Zhang, J., Zhang, Q., and Wang, M. (2025). Forsythiaside A Reduces Acetaminophen Hepatotoxic Metabolism by Inhibiting Pregnane X Receptor. Molecules, 30.","DOI":"10.3390\/molecules30051187"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"124","DOI":"10.33160\/yam.2024.05.004","article-title":"Exploring Acute Liver Damage: Slimming Health Foods and CYP3A4 Induction","volume":"67","author":"Adachi","year":"2024","journal-title":"Yonago Acta Medica"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e172632","DOI":"10.1172\/jci.insight.172632","article-title":"S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury","volume":"9","author":"Cui","year":"2024","journal-title":"JCI Insight"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"107250","DOI":"10.1016\/j.aquatox.2025.107250","article-title":"New insights into the regulation of cyp3a65 expression in transgenic tg (cyp3a65: GFP) zebrafish embryos","volume":"279","author":"Erradhouani","year":"2025","journal-title":"Aquat. Toxicol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/med.21648","article-title":"Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer","volume":"40","author":"Chai","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"113329","DOI":"10.1016\/j.envpol.2019.113329","article-title":"Pxr-and Nrf2-mediated induction of ABC transporters by heavy metal ions in zebrafish embryos","volume":"255","author":"Hu","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-022-01518-8","article-title":"Current applications and future perspective of CRISPR\/Cas9 gene editing in cancer","volume":"21","author":"Wang","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"100053","DOI":"10.1016\/j.jpet.2024.100053","article-title":"Use of an extensively humanized mouse model to predict the risk of drug\u2013drug interactions in patients receiving dexamethasone","volume":"392","author":"George","year":"2025","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"107000","DOI":"10.1016\/j.eplepsyres.2022.107000","article-title":"Functionalized PEG-PLA nanoparticles for brain targeted delivery of ketoconazole contribute to pregnane X receptor overexpressing in drug-resistant epilepsy","volume":"186","author":"Wang","year":"2022","journal-title":"Epilepsy Res."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Niu, X., Wu, T., Yin, Q., Gu, X., Li, G., Zhou, C., Ma, M., Su, L., Tang, S., and Tian, Y. (2022). Combination of paclitaxel and PXR antagonist SPA70 reverses paclitaxel-resistant non-small cell lung cancer. Cells, 11.","DOI":"10.3390\/cells11193094"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Smith, R.P., Eckalbar, W.L., Morrissey, K.M., Luizon, M.R., Hoffmann, T.J., Sun, X., Jones, S.L., Force Aldred, S., Ramamoorthy, A., and Desta, Z. (2014). Genome-wide discovery of drug-dependent human liver regulatory elements. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004648"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"7943","DOI":"10.1093\/nar\/gkq654","article-title":"ChIPing the cistrome of PXR in mouse liver","volume":"38","author":"Cui","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.bbagrm.2016.04.010","article-title":"RNA-Seq reveals common and unique PXR-and CAR-target gene signatures in the mouse liver transcriptome","volume":"1859","author":"Cui","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Regul. Mech."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"E18761429259143","DOI":"10.2174\/0118761429259143230927110556","article-title":"Dual role of pregnane X receptor in nonalcoholic fatty liver disease","volume":"17","author":"Xu","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1080\/10408398.2023.2299744","article-title":"The therapeutic potential of dietary intervention: Based on the mechanism of a tryptophan derivative-indole propionic acid on metabolic disorders","volume":"65","author":"Niu","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.jcmgh.2022.10.014","article-title":"The pregnane X receptor and indole-3-propionic acid shape the intestinal mesenchyme to restrain inflammation and fibrosis","volume":"15","author":"Flannigan","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"107121","DOI":"10.1016\/j.phrs.2024.107121","article-title":"Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor","volume":"202","author":"Peng","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Ul Ain, N., Naveed, M., Aziz, T., Shabbir, M.A., Al Asmari, F., Abdi, G., Sameeh, M.Y., and Alhhazmi, A.A. (2024). Mix-match synthesis of nanosynbiotics from probiotics and prebiotics to counter gut dysbiosis via AI integrated formulation profiling. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-69515-z"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41586-023-06906-8","article-title":"Reverse metabolomics for the discovery of chemical structures from humans","volume":"626","author":"Gentry","year":"2024","journal-title":"Nature"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s41586-023-06990-w","article-title":"Bile salt hydrolase catalyses formation of amine-conjugated bile acids","volume":"626","author":"Rimal","year":"2024","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1111\/bph.17409","article-title":"Atractylodes macrocephala Koidz polysaccharide ameliorates DSS-induced colitis in mice by regulating the gut microbiota and tryptophan metabolism","volume":"182","author":"Zhang","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1124\/dmd.123.001604","article-title":"Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16\u03b1-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes-Associated Protein Activation","volume":"52","author":"Wu","year":"2024","journal-title":"Drug Metab. Dispos."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2217\/pgs-2017-0121","article-title":"Genetic variations of the xenoreceptors NR1I2 and NR1I3 and their effect on drug disposition and response variability","volume":"19","author":"Mbatchi","year":"2018","journal-title":"Pharmacogenomics"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.2147\/DDDT.S495647","article-title":"Association of NR1I2 Polymorphism with Midazolam Clearance in Mechanically Ventilated ICU Patients: A Population Pharmacokinetic and Pharmacogenetic Study","volume":"19","author":"Xie","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41401-018-0178-4","article-title":"Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients","volume":"40","author":"Chen","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1158\/2159-8290.CD-22-1377","article-title":"N-of-1 trials in cancer drug development","volume":"13","author":"Gouda","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4274\/balkanmedj.galenos.2024.2024-9-12","article-title":"How Uremic Toxins Alter Atorvastatin Disposition: Molecular Mechanisms of Inhibition of the Enzyme CYP3A4","volume":"42","author":"Asim","year":"2025","journal-title":"Balk. Med. J."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s13318-024-00923-2","article-title":"Hypertensive Nephropathy Changes the Expression of Drug-Metabolizing Enzymes and Transporters in Spontaneously Hypertensive Rat Liver and Kidney","volume":"50","author":"Pan","year":"2025","journal-title":"Eur. J. Drug Metab. Pharmacokinet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8029\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:31:29Z","timestamp":1760034689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":170,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26168029"],"URL":"https:\/\/doi.org\/10.3390\/ijms26168029","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}