2. Academic Validation
  3. Dual FLT3 inhibitors: Against the drug resistance of acute myeloid leukemia in recent decade

Dual FLT3 inhibitors: Against the drug resistance of acute myeloid leukemia in recent decade

  • Eur J Med Chem. 2019 Sep 15:178:468-483. doi: 10.1016/j.ejmech.2019.06.002.
Ting Yuan 1,  Baowen Qi 2,  Zhongliang Jiang 3,  Wenjuan Dong 1,  Lei Zhong 1,  Lan Bai 1,  Rongsheng Tong 1,  Jiying Yu 4,  Jianyou Shi 5
Affiliations

Affiliations

  • 1 Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610072, China.
  • 2 College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, 610106, China.
  • 3 Miller School of Medicine, University of Miami, Miami, Florida, 33136, USA.
  • 4 Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610072, China. Electronic address: yujiying@163.com.
  • 5 Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu, 610072, China. Electronic address: shijianyoude@126.com.
PMID: 31207462 DOI: 10.1016/j.ejmech.2019.06.002
Abstract

Acute myeloid leukemia (AML) is a malignant disease characterized by abnormal growth and differentiation of hematopoietic stem cells. Although the pathogenesis has not been fully elucidated, many specific gene mutations have been found in AML. Fms-like tyrosine kinase 3 (FLT3) is recognized as a drug target for the treatment of AML, and the activation mutations of FLT3 were found in about 30% of AML patients. Targeted inhibition of FLT3 receptor tyrosine kinase has shown promising results in the treatment of FLT3 mutation AML. Unfortunately, the therapeutic effects of FLT3 tyrosine kinase inhibitors used as AML monotherapy are usually accompanied by the high risk of resistance development within a few months after treatment. FLT3 dual inhibitors were generated with the co-inhibition of FLT3 and another target, such as CDK4, JAK2, MEK, Mer, Pim, etc., to solve the problems mentioned above. As a result, the therapeutic effect of the drug is significantly improved, while the toxic and side effects are reduced. Besides, the life quality of AML patients with FLT3 mutation has been effectively improved. In this paper, we reviewed the studies of dual FLT3 inhibitors that have been discovered in recent years for the treatment of AML.

Keywords

Acute myeloid leukemia; Drug resistance; Dual inhibitors; FLT3.

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