2. Academic Validation
  3. Macrocyclic compounds as anti-cancer agents: design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2

Macrocyclic compounds as anti-cancer agents: design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2

  • Eur J Med Chem. 2015 May 5:95:104-15. doi: 10.1016/j.ejmech.2015.03.034.
Cheng-Qing Ning 1,  Cheng Lu 1,  Liang Hu 1,  Yan-Jing Bi 1,  Lei Yao 1,  Yu-Jun He 1,  Li-Fei Liu 1,  Xiao-Yu Liu 2,  Nie-Fang Yu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
  • 2 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China; Drug Discovery Department, Hisun Group, Taizhou 317700, China.
  • 3 School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address: niefang_yu@126.com.
PMID: 25800646 DOI: 10.1016/j.ejmech.2015.03.034
Abstract

A novel series of macrocyclic compounds were designed and synthesized as multi-target inhibitors targeting HDAC, FLT3 and JAK2. Some of these compounds exhibited potent HDAC inhibition as well as FLT3 and JAK2 inhibition under both cell-free and cellular conditions. In vitro antiproliferative assay indicated that these compounds were interestingly more cytotoxic to MV4-11 cells bearing FLT3-ITD mutation and HEL cells bearing JAK2(V617F) mutation.

Keywords

FLT3; Histone deacetylase; JAK2; Macrocyclic; Multi-target inhibitor.

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