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It is mainly caused by drug\u2010induced sensitization to UVA radiation, arising from either the drug's inherent photosensitizing potential or its interference with the metabolism of endogenous photosensitizers. A potent endogenous UVA sensitizer is 6\u2010formylindolo[3,2\u2010\n                      <jats:italic>b<\/jats:italic>\n                      ]carbazole (FICZ), a tryptophan photoproduct formed in UVB\u2010irradiated epidermal cells. By sequentially activating the aryl hydrocarbon receptor signaling pathway and inducing cytochrome P450 (CYP) 1A1 expression, FICZ induces its own degradation. Recently, we reported that the BRAF inhibitor vemurafenib interferes with CYP1A1 activity and sensitizes keratinocytes to FICZ\/UVA\u2010induced phototoxicity. Herein, we screened 12 clinical drugs, known to exhibit phototoxicity in patients, for their potential to interfere with the metabolism of (exogenous) FICZ and sensitize HaCaT keratinocytes to UVA\u2010induced phototoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The UV\u2013VIS absorption of the drugs was determined, and their effect on CYP1A1 activity and FICZ\/UVA\u2010triggered apoptosis was assessed in immortalized and primary human keratinocytes using 7\u2010ethoxyresorufin\u2010O\u2010deethylase (EROD) and caspase\u20103 activity assays. Moreover, the impact of the candidate drugs on the metabolic degradation of FICZ in cells (LC analysis) as well as on the generation of oxidative stress (MitoSOX assay, qPCR analyses) was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified two drugs, erlotinib and leflunomide, to sensitize human keratinocytes to FICZ\/UVA\u2010induced apoptosis by inhibiting CYP1A1 activity. Moreover, both drugs attenuated the metabolic breakdown of FICZ, enhanced the FICZ\/UVA\u2010triggered formation of mitochondrial superoxide anions, and increased heme oxygenase\u20101 (HMOX1) transcript levels, indicative of antioxidant defense activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Disruption of FICZ metabolism may contribute to the phototoxicity of drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/phpp.70099","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T11:06:15Z","timestamp":1780225575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Erlotinib and Leflunomide Disrupt 6\u2010Formylindolo[3,2\u2010\n                    <i>b<\/i>\n                    ]Carbazole Metabolism and Sensitize Keratinocytes to\n                    <scp>UVA<\/scp>\n                    Radiation\u2010Induced Apoptosis"],"prefix":"10.1111","volume":"42","author":[{"given":"Frederick","family":"Hartung","sequence":"first","affiliation":[{"name":"IUF \u2013 Leibniz Research Institute for Environmental Medicine  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1767-0572","authenticated-orcid":false,"given":"Julien","family":"Dairou","sequence":"additional","affiliation":[{"name":"Laboratoire De Chimie Et Biochimie Pharmacologiques Et Toxicologiques, CNRS, UMR 8601 Universit\u00e9 De Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samhita","family":"Ramamoorthy","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical Faculty Heinrich\u2010Heine\u2010University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina 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