{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:52:20Z","timestamp":1791366740498,"version":"4.3.1"},"reference-count":140,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Telomerase inhibition has emerged as a clinically relevant strategy in cancer therapy, targeting a key hallmark of tumor cell immortality. Reactivated in the majority of human cancers, telomerase enables sustained proliferation by maintaining telomere length, making it an attractive and broadly applicable therapeutic target. This review provides an updated and integrative perspective on telomerase\u2010targeted approaches, spanning small\u2010molecule inhibitors, antisense oligonucleotides, immunotherapies, and gene\u2010based strategies. Particular emphasis is placed on clinical validation, highlighting the recent regulatory approval of imetelstat and its therapeutic impact in hematologic malignancies, which represents a major milestone in translating telomerase inhibition into clinical practice. In addition, we critically evaluate emerging compounds and mechanistic classes with respect to their translational potential, selectivity, and limitations. Unlike previous reviews that primarily focus on either biological mechanisms or isolated compound classes, this work uniquely integrates medicinal chemistry insights with clinical outcomes, providing a balanced assessment of structure\u2013activity relationships alongside real\u2010world therapeutic progress. Key challenges\u2014including delayed pharmacodynamic effects, toxicity in normal proliferative tissues, and resistance\n                    <jats:italic>via<\/jats:italic>\n                    alternative lengthening of telomeres (ALT)\u2014are discussed within the context of precision oncology. Overall, this review underscores the transition of telomerase inhibition from a conceptual target to a clinically validated approach and highlights future directions for optimizing its therapeutic utility in cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70250","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:29:34Z","timestamp":1778585374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Designing Telomerase Inhibitors for Cancer Therapy: Mechanistic Insights, Medicinal Chemistry Strategies, Challenges, and Future Directions"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-6073","authenticated-orcid":false,"given":"Ahmed A.","family":"Al\u2010Karmalawy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Horus University\u2010Egypt New Damietta 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