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Drugs. 2019 Feb;79(3):331-339. doi: 10.1007/s40265-019-1062-3.
Gilteritinib (Xospata) is an orally available small molecule receptor tyrosine kinase inhibitor developed by Astellas Pharma in collaboration with Kotobuki Pharmaceutical for the treatment of acute myeloid leukaemia (AML) harbouring FMS-like tyrosine kinase 3 (FLT3) mutations. Gilteritinib inhibits FLT3 (STK1 or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246). Gilteritinib inhibits FLT3 signalling in cells expressing FLT3 internal tandem duplication (ITD), tyrosine kinase domain mutation FLT3-D835Y and the double mutant FLT3-ITD-D835Y, thereby inducing apoptosis. Gilteritinib also binds to and inhibits the wild-type and mutated forms of ALK, resulting in reduced tumour cell proliferation in cancer cell types that overexpress the mutation. Gilteritinib is approved in Japan for the treatment of relapsed or refractory AML with FLT3 mutation. Recently, it was also approved in the USA for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation, as detected by an FDA-approved test. Clinical development of gilteritinib is underway in several countries worldwide. Development for non-small cell lung cancer and solid tumours has been discontinued.
吉特替尼（Xospata）是一种口服小分子受体酪氨酸激酶抑制剂，由安斯泰来制药公司与日本化药株式会社合作开发，用于治疗携带 FMS 样酪氨酸激酶 3（FLT3）突变的急性髓系白血病（AML）。吉特替尼抑制 FLT3（STK1 或 FLK2）、AXL（UFO 或 JTK11）和间变性淋巴瘤激酶（ALK 或 CD246）。吉特替尼在表达 FLT3 内部串联重复（ITD）、酪氨酸激酶结构域突变 FLT3-D835Y 和双突变 FLT3-ITD-D835Y 的细胞中抑制 FLT3 信号传导，从而诱导细胞凋亡。吉特替尼还结合并抑制野生型和突变型 ALK，从而减少过度表达突变的癌细胞类型中的肿瘤细胞增殖。吉特替尼在日本被批准用于治疗具有 FLT3 突变的复发性或难治性 AML。最近，它还在美国被批准用于治疗通过 FDA 批准的检测方法检测到具有 FLT3 突变的复发性或难治性 AML 的成年患者。吉特替尼在全球多个国家的临床开发正在进行中。用于非小细胞肺癌和实体瘤的开发已被停止。
