Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML

Zoltán Nemes, Krisztina Takács-Novák, Gergely Völgyi, Klara Valko, Szabolcs Béni, Zoltán Horváth, Bálint Szokol, Nóra Breza, Judit Dobos, Csaba Szántai-Kis, Eszter Illyés, Sándor Boros, Robbert Jan Kok, László Őrfi

Research output: Contribution to journalArticle

2 Citations (Scopus)


Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration.

Original languageEnglish
Pages (from-to)2391-2398
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Issue number14
Publication statusPublished - Aug 1 2018


  • Acute myeloid leukemia
  • Chromatographic Hydrophobicity Index
  • FLT3-ITD kinase inhibitior
  • Peptide based targeted delivery
  • Shake-flask partition coefficient determination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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