1. Academic Validation
  2. Suramin derivatives play an important role in blocking the interaction between FGF1 and FGFRD2 to inhibit cell proliferation

Suramin derivatives play an important role in blocking the interaction between FGF1 and FGFRD2 to inhibit cell proliferation

  • Eur J Med Chem. 2020 Nov 15:206:112656. doi: 10.1016/j.ejmech.2020.112656.
Nuzhat Parveen 1 Yan-Liang Lin 2 Md Imran Khan 3 Ruey-Hwang Chou 4 Chung-Ming Sun 5 Chin Yu 6
Affiliations

Affiliations

  • 1 Chemistry Department, National Tsing Hua University, Hsinchu, 300, Taiwan.
  • 2 Department of Applied Chemistry, National Chiao Tung University, Hsinchu, 300, Taiwan.
  • 3 Department of Physics, University of Central Florida, Orlando, 32816, Florida, USA.
  • 4 Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, 404, Taiwan; Department of Biotechnology, Asia University, Taichung, 40402, Taiwan.
  • 5 Department of Applied Chemistry, National Chiao Tung University, Hsinchu, 300, Taiwan; Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
  • 6 Chemistry Department, National Tsing Hua University, Hsinchu, 300, Taiwan. Electronic address: cyu.nthu@gmail.com.
Abstract

The inhibition of protein function by small compounds plays a critical role in controlling cell proliferation. We report on a new class of small molecule (NCTU-Alan-2026) inhibitors for cell proliferation. NCTU-Alan-2026 blocks the interaction between FGF1 and its receptor FGF1R2D2. Extensive NMR studies combined with fluorescence experiments provided the specific mechanism of how NCTU-Alan-2026 could inhibit cell proliferation. We describe an innovative therapeutic approach for anti-proliferation and demonstrate an example of inhibition of small molecules by blocking the protein-protein interaction. We found that the compound NCTU-Alan-2026 blocked the interaction between the two proteins FGF1 and FGF1R2D2 and inhibited cell proliferation. The toxicity of NCTU-Alan-2026 is lower than that of suramin. Thus, NCTU-Alan-2026 could be a better drug than suramin in the treatment of Cancer.

Keywords

Cell proliferation; FGF1; HSQC; Haddock; NCTU-Alan-2026; Protein-drug interactions; Toxicity; WST1assay.

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