2. Academic Validation
  3. Design, synthesis and biological evaluation of a novel non-Gemini analog of UVB1 and crystal structure of its complex with the vitamin D receptor

Design, synthesis and biological evaluation of a novel non-Gemini analog of UVB1 and crystal structure of its complex with the vitamin D receptor

  • Bioorg Chem. 2025 Feb 4:157:108239. doi: 10.1016/j.bioorg.2025.108239.
Uxía Gómez-Bouzó 1,  Carole Peluso-Iltis 2,  Hugo Santalla 1,  Lieve Verlinden 3,  Annemieke Verstuyf 3,  Natacha Rochel 4,  Generosa Gómez 5,  Yagamare Fall 6
Affiliations

Affiliations

  • 1 Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain.
  • 2 Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67400 France; CNRS UMR 7104, Illkirch 67400 France; Inserm U1258, Illkirch 67400 France; University of Strasbourg, Illkirch 67400 France.
  • 3 Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven 3000 Leuven, Belgium.
  • 4 Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67400 France; CNRS UMR 7104, Illkirch 67400 France; Inserm U1258, Illkirch 67400 France; University of Strasbourg, Illkirch 67400 France. Electronic address: rochel@igbmc.fr.
  • 5 Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain. Electronic address: ggomez@uvigo.es.
  • 6 Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain. Electronic address: yagamare@uvigo.es.
PMID: 39938446 DOI: 10.1016/j.bioorg.2025.108239
Abstract

We synthesized UG-650, a novel non-Gemini analog of UVB1 that combines structural features of UVB1 and MC 1288. The evaluation of the bioactivities indicates that UG-650 dose-dependently inhibited MCF-7 cell proliferation. In comparison to calcitriol, slightly lower concentrations of UG-650 were needed to achieve equivalent levels of proliferation inhibition. Structural analysis revealed that the analog forms additional interactions stabilizing VDR active form.

Keywords

Antiproliferative agents; Calcitriol; Cancer; Gemini; Hypercalcemia.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-170975
    UVB1 Non-Gemini Analog