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Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2017

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs

Résumé

Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A series of dual-target compounds were designed and synthesized incorporating a sulfonamide, sulfamide, or sulfamate moiety combined with several different anti-cancer drugs, including the chemotherapeutic agents chlorambucil, tirapazamine, and temozolomide, two Ataxia Telangiectasia and Rad3-related protein inhibitors (ATRi), and the antidiabetic biguanide agent phenformin. An ATRi derivative (12) was the only compound to show a preferred efficacy in CAIX overexpressing cells versus cells without CAIX expression when combined with radiation. Its efficacy might however not solely depend on binding to CAIX, since all described compounds generally display low activity as carbonic anhydrase inhibitors. The hypothesis that dualtarget compounds specifically target CAIX expressing tumor cells was therefore not confirmed. Even though dual-target compounds remain an interesting approach, alternative options should also be investigated as novel treatment strategies.

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Chimie
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Dates et versions

hal-03621627 , version 1 (28-03-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Simon van Kuijk, Nanda Kumar Parvathaneni, Raymon Niemans, Marike van Gisbergen, Fabrizio Carta, et al.. New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs. European Journal of Medicinal Chemistry, 2017, 127, pp.691 - 702. ⟨10.1016/j.ejmech.2016.10.037⟩. ⟨hal-03621627⟩
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