Levis Mark, Small Donald
Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, MD 21231-1000, USA.
Expert Opin Investig Drugs. 2003 Dec;12(12):1951-62. doi: 10.1517/13543784.12.12.1951.
Acute myeloid leukaemia (AML) is an aggressive haematological malignancy that is curable in approximately 40% of cases. Activating mutations of the receptor tyrosine kinase FLT3 (FMS-like tyrosine kinase-3) are the single most common molecular abnormalities in AML and are associated with a distinctly worse prognosis. In an effort to target this mutation and improve outcomes in this subgroup of AML patients, several novel small-molecule FLT3 tyrosine kinase inhibitors are currently in development. Some of these FLT3 inhibitors are useful only as laboratory tools, while others clearly have clinical potential. These compounds are derived from a wide variety of chemical classes and differ significantly both in their potency and selectivity. This review summarises these developments and examines these novel agents with regard to both the assays used to characterise them and their clinical potential.
急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤，约40%的病例可治愈。受体酪氨酸激酶FLT3（FMS样酪氨酸激酶3）的激活突变是AML中最常见的单一分子异常，且与明显更差的预后相关。为了靶向这种突变并改善AML患者这一亚组的治疗结果，目前有几种新型小分子FLT3酪氨酸激酶抑制剂正在研发中。其中一些FLT3抑制剂仅用作实验室工具，而其他一些显然具有临床潜力。这些化合物源自多种化学类别，其效力和选择性差异很大。本综述总结了这些进展，并从用于表征它们的检测方法及其临床潜力方面对这些新型药物进行了研究。
