{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:45:31Z","timestamp":1783435531482,"version":"3.54.6"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010105","name":"Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat","doi-asserted-by":"publisher","award":["102-5212\/18-3000"],"award-info":[{"award-number":["102-5212\/18-3000"]}],"id":[{"id":"10.13039\/100010105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemotherapy resistance, particularly multidrug resistance (MDR), remains a significant barrier to effective cancer treatment, leading to high mortality rates. The development of novel therapeutic strategies targeting key molecular mechanisms to counteract drug resistance is thus an urgent clinical need. In this study, we evaluated the potential of the small molecule SCO-101 to restore chemotherapy sensitivity in drug-resistant cancer cells. Using in silico and in vitro models such as molecular docking, cell viability, colony formation, dye efflux, transporter assays and chemotherapy retention, we assessed the impact of SCO-101 on drug retention and response in several drug-resistant cancer cells. SCO-101 was found to inhibit the activity of breast cancer resistance protein (BCRP\/ABCG2) and UDP Glucuronosyltransferase Family 1 Member A1 (UGT1A1), two key proteins involved in drug resistance by cellular drug excretion and drug metabolism. Our results demonstrate that inhibition of these proteins by SCO-101 leads to increased intracellular drug accumulation, enhancing the cytotoxic effects of chemotherapy agents. Additionally, we identified a strong correlation between high ABCG2 expression and MDR in non-drug-resistant models, where cells exhibiting elevated ABCG2 levels displayed chemotherapy resistance, which was effectively reversed by SCO-101 co-treatment. These findings highlight the therapeutic potential of SCO-101 in overcoming MDR by inhibiting drug efflux mechanisms and metabolism, thereby enhancing chemotherapy efficacy. SCO-101 is currently undergoing clinical trials as an orally administered drug and is considered a promising strategy for improving cancer treatment outcomes in patients with drug-resistant tumors.<\/jats:p>","DOI":"10.3390\/ijms26083790","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:16:21Z","timestamp":1744863381000},"page":"3790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of ABCG2 by SCO-101 Enhances Chemotherapy Efficacy in Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Anamarija","family":"Pfeiffer","sequence":"first","affiliation":[{"name":"Biognosys AG, 8952 Schlieren, Switzerland"},{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2419-2196","authenticated-orcid":false,"given":"Luca","family":"Di Leo","sequence":"additional","affiliation":[{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-7378","authenticated-orcid":false,"given":"Marc Baker","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubeen","family":"Nawabi","sequence":"additional","affiliation":[{"name":"Genmab A\/S, Carl Jacobsens Vej 30, 2500 Valby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Ambj\u00f8rner","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diba","family":"Ardeshir-Larijani","sequence":"additional","affiliation":[{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, Denmark"},{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Thybo","family":"Colstrup","sequence":"additional","affiliation":[{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, Denmark"},{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9859-6093","authenticated-orcid":false,"given":"Signe Vedel","family":"Borchert","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Saaby","sequence":"additional","affiliation":[{"name":"Bioneer A\/S, Kogle Alle 2, 2970 H\u00f8rsholm, Denmark"},{"name":"Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0823-1220","authenticated-orcid":false,"given":"Birger","family":"Brodin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-2287","authenticated-orcid":false,"given":"Michael","family":"Gajhede","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-8952","authenticated-orcid":false,"given":"Xamuel Loft","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark"},{"name":"Institut Laue\u2013Langevin, 71 Avenue de Martyrs, 38042 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"\u010ce\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Br\u00fcnner","sequence":"additional","affiliation":[{"name":"Scandion Oncology A\/S, Symbion, 2100 Copenhagen, 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Cancer J. Clin."},{"key":"ref_2","unstructured":"International Agency for Research on Cancer (2025, January 20). Estimated Number of Deaths from 2022 to 2050, Both Sexes, Age [0\u201385+]. Available online: https:\/\/gco.iarc.fr\/tomorrow\/en\/dataviz\/isotype?types=1&single_unit=500000&years=2050."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrc2714","article-title":"Environment-mediated drug resistance: A major contributor to minimal residual disease","volume":"9","author":"Meads","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A view on drug resistance in cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ramos, A., Sadeghi, S., and Tabatabaeian, H. (2021). Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179451"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature24297","article-title":"Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition","volume":"551","author":"Hangauer","year":"2017","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1002\/cncr.30435","article-title":"Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma","volume":"123","author":"Lim","year":"2017","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.cell.2018.06.025","article-title":"Toward Minimal Residual Disease-Directed Therapy in Melanoma","volume":"174","author":"Rambow","year":"2018","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cree, I.A., and Charlton, P. (2017). Molecular chess? Hallmarks of anti-cancer drug resistance. BMC Cancer, 17.","DOI":"10.1186\/s12885-016-2999-1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/ijc.20032","article-title":"ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases","volume":"109","author":"Candeil","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_12","first-page":"4618","article-title":"MDR1 gene overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment","volume":"6","author":"Tada","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev.pharmtox.39.1.361","article-title":"Biochemical, cellular, and pharmacological aspects of the multidrug transporter","volume":"39","author":"Ambudkar","year":"1999","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.bcp.2005.06.018","article-title":"Expression of the drug transporters MDR1\/ABCB1, MRP1\/ABCC1, MRP2\/ABCC2, BCRP\/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver","volume":"70","author":"Albermann","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev-biophys-111622-091232","article-title":"Structure and Mechanism of Human ABC Transporters","volume":"52","author":"Alam","year":"2023","journal-title":"Annu. Rev. Biophys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug resistance in cancer: Role of ATP-dependent transporters","volume":"2","author":"Gottesman","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrc2789","article-title":"ABC transporters in cancer: More than just drug efflux pumps","volume":"10","author":"Fletcher","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41568-018-0005-8","article-title":"Revisiting the role of ABC transporters in multidrug-resistant cancer","volume":"18","author":"Robey","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103537","DOI":"10.1016\/j.drudis.2023.103537","article-title":"ATP-binding cassette efflux transporters and MDR in cancer","volume":"28","author":"Pote","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.trecan.2023.09.013","article-title":"Linking ABC transporters to the hallmarks of cancer","volume":"10","author":"Duvivier","year":"2024","journal-title":"Trends Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114542","DOI":"10.1016\/j.ejmech.2022.114542","article-title":"Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update","volume":"239","author":"Engle","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108488","DOI":"10.1016\/j.pharmthera.2023.108488","article-title":"Strategies to overcome cancer multidrug resistance (MDR) through targeting P-glycoprotein (ABCB1): An updated review","volume":"249","author":"Dong","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-pharmtox-011613-135959","article-title":"Targeting multidrug resistance protein 1 (MRP1, ABCC1): Past, present, and future","volume":"54","author":"Cole","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100795","DOI":"10.1016\/j.drup.2021.100795","article-title":"Targeting multidrug resistance-associated protein 1 (MRP1)-expressing cancers: Beyond pharmacological inhibition","volume":"59","author":"Hanssen","year":"2021","journal-title":"Drug Resist. Updates"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10555-007-9042-6","article-title":"ABCG2: Determining its relevance in clinical drug resistance","volume":"26","author":"Robey","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1124\/mol.113.088609","article-title":"Molecular pharmacology of ABCG2 and its role in chemoresistance","volume":"84","author":"Stacy","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.febslet.2004.03.123","article-title":"ABCG2\u2014A transporter for all seasons","volume":"567","author":"Sarkadi","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kathawala, R.J., Espitia, C.M., Jones, T.M., Islam, S., Gupta, P., Zhang, Y.K., Chen, Z.S., Carew, J.S., and Nawrocki, S.T. (2020). ABCG2 Overexpression Contributes to Pevonedistat Resistance. Cancers, 12.","DOI":"10.3390\/cancers12020429"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41416-019-0722-0","article-title":"Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression","volume":"122","author":"Allain","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_30","first-page":"61","article-title":"UGT1A1 polymorphisms in cancer: Impact on irinotecan treatment","volume":"10","author":"Takano","year":"2017","journal-title":"Pharmgenomics Pers. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nelson, R.S., Seligson, N.D., Bottiglieri, S., Carballido, E., Cueto, A.D., Imanirad, I., Levine, R., Parker, A.S., Swain, S.M., and Tillman, E.M. (2021). UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation. Cancers, 13.","DOI":"10.3390\/cancers13071566"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lai, J.I., Tseng, Y.J., Chen, M.H., Huang, C.F., and Chang, P.M. (2020). Clinical Perspective of FDA Approved Drugs With P-Glycoprotein Inhibition Activities for Potential Cancer Therapeutics. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.561936"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Toyoda, Y., Takada, T., and Suzuki, H. (2019). Inhibitors of Human ABCG2: From Technical Background to Recent Updates With Clinical Implications. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00208"},{"key":"ref_34","unstructured":"A\/S, S.O. (2025, February 10). A Phase 2 Trial of SCO-101 in Combination with FOLFIRI for Patients with Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04247256?cond=Cancer&term=sco-101&rank=1."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00232-003-0627-x","article-title":"Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293 cells by acidic di-aryl-ureas","volume":"196","author":"Helix","year":"2003","journal-title":"J. Membr. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105315","DOI":"10.1016\/j.ejps.2020.105315","article-title":"Pharmacodynamic modelling reveals synergistic interaction between docetaxel and SCO-101 in a docetaxel-resistant triple negative breast cancer cell line","volume":"148","author":"Bagger","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/bcpt.13466","article-title":"Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO-101 in adult male and female volunteers","volume":"127","author":"Bergmann","year":"2020","journal-title":"Basic. Clin. Pharmacol. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.molonc.2015.02.008","article-title":"Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance","volume":"9","author":"Jensen","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111858","DOI":"10.1016\/j.yexcr.2020.111858","article-title":"Overexpression of ABCG2 confers resistance to pevonedistat, an NAE inhibitor","volume":"388","author":"Wei","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1158\/0008-5472.CAN-09-3367","article-title":"Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan","volume":"70","author":"Zander","year":"2010","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sorf, A., Sucha, S., Morell, A., Novotna, E., Staud, F., Zavrelova, A., Visek, B., Wsol, V., and Ceckova, M. (2020). Targeting Pharmacokinetic Drug Resistance in Acute Myeloid Leukemia Cells with CDK4\/6 Inhibitors. Cancers, 12.","DOI":"10.3390\/cancers12061596"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sucha, S., Sorf, A., Svoren, M., Vagiannis, D., Ahmed, F., Visek, B., and Ceckova, M. (2022). ABCB1 as a potential beneficial target of midostaurin in acute myeloid leukemia. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.112962"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e11171","DOI":"10.1016\/j.heliyon.2022.e11171","article-title":"P-glycoprotein and cancer: What do we currently know?","volume":"8","author":"Muriithi","year":"2022","journal-title":"Heliyon"},{"key":"ref_45","first-page":"1","article-title":"Human ABCG2: Structure, function, and its role in multidrug resistance","volume":"3","author":"Mo","year":"2012","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1177\/1087057105284576","article-title":"A high-throughput cell-based assay for inhibitors of ABCG2 activity","volume":"11","author":"Henrich","year":"2006","journal-title":"J. Biomol. Screen."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1158\/1535-7163.MCT-07-0352","article-title":"New inhibitors of ABCG2 identified by high-throughput screening","volume":"6","author":"Henrich","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Le, M.T., Hoang, V.N., Nguyen, D.N., Bui, T.H., Phan, T.V., Huynh, P.N., Tran, T.D., and Thai, K.M. (2021). Structure-Based Discovery of ABCG2 Inhibitors: A Homology Protein-Based Pharmacophore Modeling and Molecular Docking Approach. Molecules, 26.","DOI":"10.3390\/molecules26113115"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1158\/0008-5472.CAN-04-1817","article-title":"Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2","volume":"65","author":"Pozza","year":"2005","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1124\/mol.65.5.1208","article-title":"Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport","volume":"65","author":"Zhang","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_51","first-page":"417","article-title":"Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C","volume":"1","author":"Allen","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/cpt.903","article-title":"Reverse Translational Research of ABCG2 (BCRP) in Human Disease and Drug Response","volume":"103","author":"Brackman","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.3748\/wjg.v24.i29.3222","article-title":"ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?","volume":"24","author":"Adamska","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_54","unstructured":"(2025, February 10). Scandion Oncology A\/S Scandion Oncology Reports Promising Updated Phase II CORIST Data, Including Topline Overall Survival. Available online: https:\/\/storage.mfn.se\/0bae93eb-3725-4176-9faa-2d2197a23dbe\/scandion-oncology-reports-promising-updated-corist-phase-ii-data.pdf."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jmb.2018.11.007","article-title":"Overcoming Drug Resistance through the Development of Selective Inhibitors of UDP-Glucuronosyltransferase Enzymes","volume":"431","author":"Osborne","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/1479-7364-4-4-238","article-title":"The clinical application of UGT1A1 pharmacogenetic testing: Gene-environment interactions","volume":"4","author":"Marques","year":"2010","journal-title":"Hum. Genom."},{"key":"ref_57","unstructured":"Vestlev, P.M. (2025, February 10). Clinical Trial to Investigate Safety, Tolerability and MTD for SCO-101 in Combination with Gemcitabine and Nab-paclitaxel in Inoperable Pancreatic Cancer Patients. (PANTAX-Ib), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04652206?term=pantax&rank=1."},{"key":"ref_58","unstructured":"(2025, January 13). Scandion Oncology A\/S Scandion Oncology Announces Final Data from the CORIST Trial and Is Ready to Move into a Randomized Phase II Proof of Concept Trial in Colorectal Cancer. Available online: https:\/\/scandiononcology.com\/mfn_news\/scandion-oncology-announces-final-data-from-the-corist-trial-and-is-ready-to-move-into-a-randomized-phase-ii-proof-of-concept-trial-in-colorectal-cancer\/."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41594-018-0049-1","article-title":"Structural basis of small-molecule inhibition of human multidrug transporter ABCG2","volume":"25","author":"Jackson","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ambjorner, S.E.B., Wiese, M., Kohler, S.C., Svindt, J., Lund, X.L., Gajhede, M., Saaby, L., Brodin, B., Rump, S., and Weigt, H. (2020). The Pyrazolo [3,4-d]pyrimidine Derivative, SCO-201, Reverses Multidrug Resistance Mediated by ABCG2\/BCRP. Cells, 9.","DOI":"10.3390\/cells9030613"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Petersen, M.J., Lund, X.L., Semple, S.J., Buirchell, B., Franzyk, H., Gajhede, M., Kongstad, K.T., Stenvang, J., and Staerk, D. (2021). Reversal of ABCG2\/BCRP-Mediated Multidrug Resistance by 5,3\u2032,5\u2032-Trihydroxy-3,6,7,4\u2032-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock. Biomolecules, 11.","DOI":"10.3390\/biom11101534"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing (SC06), Tampa, FL, USA.","DOI":"10.1109\/SC.2006.54"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3790\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:16:08Z","timestamp":1760030168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":66,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083790"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083790","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]}}}