Gilteritinib: First Global Approval
Gilteritinib: First Global Approval
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DOI：
10.1007/s40265-019-1062-3
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发表时间：
2019-02-01
期刊：
影响因子：
11.5
通讯作者：
Dhillon, Sohita
中科院分区：
文献类型：
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作者：
Dhillon, Sohita
Gilteritinib（Xospata（R））是一种口服小分子受体酪氨酸激酶抑制剂，由Astellas Pharma与Kotobuki Pharmaceutical合作开发，用于治疗携带FMS样酪氨酸激酶3（FLT 3）突变的急性髓性白血病（AML）。Gilteritinib可抑制FLT 3（STK 1或FLK 2）、AXL（UFO或JTK 11）和间变性淋巴瘤激酶（ALK或CD 246）。Gilteritinib抑制表达FLT 3内部串联重复（ITD）、酪氨酸激酶结构域突变FLT 3-D835 Y和双突变FLT 3-ITD-D835 Y的细胞中的FLT 3信号传导，从而诱导细胞凋亡。Gilteritinib还可结合并抑制ALK的野生型和突变形式，导致过表达突变的癌细胞类型中肿瘤细胞增殖减少。Gilteritinib在日本获批用于治疗FLT 3突变的复发性或难治性AML。最近，它也在美国被批准用于治疗患有FLT 3突变的复发性或难治性AML的成人患者，如FDA批准的测试所检测到的。gilteritinib的临床开发正在全球多个国家进行。非小细胞肺癌和实体瘤的开发已经停止。
Gilteritinib (Xospata((R))) 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.