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
  • 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: [email protected].
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.