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近年来,临床上已批准的用于治疗髓系白血病的小分子药物的进展。

Recent advance of clinically approved small-molecule drugs for the treatment of myeloid leukemia.

机构信息

Department of Pharmacy, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.

First People's Hospital of Shangqiu, Henan Province, Shangqiu, 476100, China; Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun, 130033, China.

出版信息

Eur J Med Chem. 2023 Dec 5;261:115827. doi: 10.1016/j.ejmech.2023.115827. Epub 2023 Sep 22.

Abstract

Myeloid leukemia denotes a hematologic malignancy characterized by aberrant proliferation and impaired differentiation of blood progenitor cells within the bone marrow. Despite the availability of several treatment options, the clinical outlook for individuals afflicted with myeloid leukemia continues to be unfavorable, making it a challenging disease to manage. Over the past, substantial endeavors have been dedicated to the identification of novel targets and the advancement of enhanced therapeutic modalities to ameliorate the management of this disease, resulting in the discovery of many clinically approved small-molecule drugs for myeloid leukemia, including histone deacetylase inhibitors, hypomethylating agents, and tyrosine kinase inhibitors. This comprehensive review succinctly presents an up-to-date assessment of the application and synthetic routes of clinically sanctioned small-molecule drugs employed in the treatment of myeloid leukemia. Additionally, it provides a concise exploration of the pertinent challenges and prospects encompassing drug resistance and toxicity. Overall, this review effectively underscores the considerable promise exhibited by clinically endorsed small-molecule drugs in the therapeutic realm of myeloid leukemia, while concurrently shedding light on the prospective avenues that may shape the future landscape of drug development within this domain.

摘要

髓系白血病是一种血液系统恶性肿瘤,其特征是骨髓中血液祖细胞的异常增殖和分化障碍。尽管有几种治疗选择,但患有髓系白血病的个体的临床前景仍然不佳,因此这种疾病的治疗极具挑战性。过去,人们致力于发现新的靶点和推进增强的治疗方法,以改善这种疾病的管理,从而发现了许多临床上批准用于髓系白血病的小分子药物,包括组蛋白去乙酰化酶抑制剂、低甲基化剂和酪氨酸激酶抑制剂。本综述简要介绍了临床上批准用于治疗髓系白血病的小分子药物的应用和合成途径的最新评估。此外,还简要探讨了包括耐药性和毒性在内的相关挑战和前景。总的来说,这篇综述有效地强调了临床上认可的小分子药物在髓系白血病治疗领域的巨大潜力,同时也揭示了可能塑造该领域药物开发未来格局的有前途的途径。

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