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Indole\/azaindole is a privileged heterocyclic scaffold in medicinal chemistry with versatile structural modification potential and inherent antileukemic bioactivity. Rational hybridization of indole\/azaindole with diverse pharmacophores has become a core strategy for developing novel antileukemic agents, thereby enabling synergistic efficacy, reversal of drug resistance, and reduced toxicity. This review systematically summarizes the research progress of indole\u2010based hybrids and closely related indole bioisosteres (azaindole hybrids) with antileukemic activity from 2021 to the present. Distinct from previous descriptive reviews, we stratified all candidate compounds by evidence hierarchy: in vitro antiproliferative activity, molecular mechanistic validation, and in vivo preclinical efficacy. This work focuses on structure\u2010activity relationships (SARs), multi\u2010target mechanisms, and preclinical pharmacological characteristics of indole\u2010 and azaindole\u2010based antileukemic hybrids, aiming to provide targeted guidance for the rational design and clinical translation of novel indole\u2010 and azaindole\u2010based antileukemic drugs.<\/jats:p>","DOI":"10.1002\/ardp.70307","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:31:58Z","timestamp":1783924318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Indole and Azaindole Hybrid Agents for Leukemia Therapy: Recent Research Advances and Therapeutic Potential"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4776-4790","authenticated-orcid":false,"given":"Yanjing","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danchen","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health and Nursing, Xianning Medical College Hubei University of Science and Technology Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5316-2621","authenticated-orcid":false,"given":"Yafei","family":"Zhuang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xianning Medical College Hubei University of Science and Technology Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00864-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101154"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02452-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-022-03460-y"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpmed.2025.03.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpmed.2025.03.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00355-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2024.101196"},{"issue":"2","key":"e_1_2_10_10_1","first-page":"130","article-title":"Advances and Future Goals in Acute Myeloid Leukaemia Therapy","volume":"18","author":"Bittar G.","year":"2022","journal-title":"Oncology & Haematology"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000547506"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115701786351199241112163708"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2025.100208"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2521250"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.108092"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.70156"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112359"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2521250"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.118449"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2026.118583"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.70187"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.6023\/cjoc202008057"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18020275"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108677"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400437"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116352"},{"issue":"6","key":"e_1_2_10_27_1","first-page":"1","article-title":"New 1,4\u2010Dihydropyrazolo[4,3\u2010b]Indoles Induce Antiproliferation of Acute Myeloid Leukemia Cells and Inhibition of Selective Inflammatory Cytokines","volume":"17","author":"Binh V. 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