{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:01:32Z","timestamp":1785142892876,"version":"3.55.0"},"reference-count":88,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Colorectal cancer (CRC) represents one of the most prevalent and lethal malignancies worldwide, with rapidly increasing global incidence and mortality. Current clinical therapies for CRC are severely compromised by tumor metastasis, intrinsic and acquired drug resistance, and unsatisfactory prognosis for advanced patients, highlighting an urgent demand for novel and effective therapeutic candidates. As privileged multifunctional scaffolds, indole hybrids integrate diverse pharmacophores to achieve simultaneous modulation of multiple CRC\u2010associated oncogenic signaling pathways and mutant proteins, enabling them to overcome the limitations of traditional single\u2010target drugs, reduce systemic toxicity, and optimize pharmacokinetic performance. This review comprehensively summarizes the research progress of novel indole hybrids for anti\u2010CRC therapy reported since 2021, excluding indole\u2013pyrimidine and indole\u2013pyridine hybrids covered in previous studies. Notably, among all summarized subclasses, indole\u2013chalcone\/chromene, indole\u2013hydroxamic acid\/benzamide, and indole\u2013azole hybrids, show the most prominent and promising therapeutic outcomes. These three dominant hybrid categories display potent antiproliferative activity against both drug\u2010sensitive and drug\u2010resistant CRC cell lines, exert robust in vivo tumor growth inhibition in xenograft models, and possess favorable safety profiles with low cytotoxicity to normal cells. We systematically elaborate their key structure\u2013activity relationships, core anti\u2010CRC molecular mechanisms, including cell cycle arrest, apoptosis induction, and targeted pathway regulation, as well as superior preclinical pharmacological characteristics. Furthermore, the current challenges and future research directions for indole hybrid\u2010based anti\u2010CRC drug development are discussed.<\/jats:p>","DOI":"10.1002\/ardp.70301","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:56:02Z","timestamp":1783428962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent Progress and Therapeutic Potential of Indole Hybrids Against Colorectal Cancer"],"prefix":"10.1002","volume":"359","author":[{"given":"Danchen","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesong","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning Hubei 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