2. Academic Validation
  3. A cyanine-based NIR fluorescent Vemurafenib analog to probe BRAFV600E in cancer cells

A cyanine-based NIR fluorescent Vemurafenib analog to probe BRAFV600E in cancer cells

  • Eur J Med Chem. 2023 Aug 5;256:115446. doi: 10.1016/j.ejmech.2023.115446.
Elisabetta Barresi 1,  Caterina Baldanzi 2,  Marta Roncetti 3,  Michele Roggia 4,  Emma Baglini 5,  Irene Lepori 6,  Marianna Vitiello 2,  Silvia Salerno 1,  Lorena Tedeschi 7,  Federico Da Settimo 1,  Sandro Cosconati 4,  Laura Poliseno 8,  Sabrina Taliani 9
Affiliations

Affiliations

  • 1 Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126, Pisa, Italy.
  • 2 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy; Oncogenomics Unit, Core Research Laboratory, ISPRO, Via Moruzzi 1, 56124, Pisa, Italy.
  • 3 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy; Oncogenomics Unit, Core Research Laboratory, ISPRO, Via Moruzzi 1, 56124, Pisa, Italy; University of Siena, Siena, Italy.
  • 4 DiSTABiF, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy.
  • 5 Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
  • 6 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy; Oncogenomics Unit, Core Research Laboratory, ISPRO, Via Moruzzi 1, 56124, Pisa, Italy; Department of Microbiology, University of Massachusetts, Amherst, MA, USA.
  • 7 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy.
  • 8 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy; Oncogenomics Unit, Core Research Laboratory, ISPRO, Via Moruzzi 1, 56124, Pisa, Italy. Electronic address: [email protected].
  • 9 Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy; Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126, Pisa, Italy. Electronic address: [email protected].
PMID: 37182332 DOI: 10.1016/j.ejmech.2023.115446
Abstract

BRaf represents one of the most frequently mutated protein kinase genes and BRafV600E mutation may be found in many types of Cancer, including hairy cell leukemia (HCL), anaplastic thyroid Cancer (ATC), colorectal Cancer and melanoma. Herein, a fluorescent probe, based on the structure of the highly specific BRafV600E inhibitor Vemurafenib (Vem, 1) and featuring the NIR fluorophore cyanine-5 (Cy5), was straightforwardly synthesized and characterized (Vem-L-Cy5, 3), showing promising spectroscopic properties. Biological validation in BRafV600E-mutated Cancer cells evidenced the ability of 3 to penetrate inside the cells, specifically binding to its elective target BRafV600E with high affinity, and inhibiting MEK phosphorylation and cell growth with a potency comparable to that of native Vem 1. Taken together, these data highlight Vem-L-Cy5 3 as a useful tool to probe BRafV600E mutation in Cancer cells, and suitable to acquire precious insights for future developments of more informed BRaf inhibitors-centered therapeutic strategies.

Keywords

BRAF(V600E); Cyanine-5; Fluorescent probe; Hairy cell leukemia; Melanoma; Vemurafenib.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-149380
    BRAF Inhibitor
    Raf