Acharya Baku, Saha Debasmita, Armstrong Daniel, Lakkaniga Naga Rajiv, Frett Brendan
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences Little Rock AR 72205 USA
Department of Chemistry and Chemical Biology, Indian Institute of Technology (Indian School of Mines) Dhanbad Jharkhand 826004 India.
RSC Med Chem. 2022 May 23;13(7):798-816. doi: 10.1039/d2md00067a. eCollection 2022 Jul 20.
FLT3 mutations are one of the most common genetic aberrations found in nearly 30% of acute myeloid leukemias (AML). The mutations are associated with poor prognosis despite advances in the understanding of the biological mechanisms of AML. Numerous small molecule FLT3 inhibitors have been developed in an effort to combat AML. Even with the development of these inhibitors, the five-year overall survival for newly diagnosed AML is less than 30%. In 2017, midostaurin received FDA approval to treat AML, which was the first approved FLT3 inhibitor in the U.S. and Europe. Following, gilteritinib received FDA approval in 2018 and in 2019 quizartinib received approval in Japan. This review parallels these clinical success stories along with other pre-clinical and clinical investigations of FLT3 inhibitors.
FLT3突变是在近30%的急性髓系白血病（AML）中发现的最常见的基因畸变之一。尽管对AML生物学机制的理解有所进展，但这些突变与不良预后相关。为了对抗AML，已经开发了许多小分子FLT3抑制剂。即使有了这些抑制剂，新诊断AML的五年总生存率仍低于30%。2017年，米哚妥林获得美国食品药品监督管理局（FDA）批准用于治疗AML，这是美国和欧洲首个获批的FLT3抑制剂。随后，吉瑞替尼于2018年获得FDA批准，Quizartinib于2019年在日本获得批准。本综述将这些临床成功案例与FLT3抑制剂的其他临床前和临床研究进行了对比。
