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  • Title: Disruption of SSBs repair to combat platinum resistance via the JWA-targeted Pt(IV) prodrug conjugated with a wogonin derivative.
    Author: Wang X, Li L, Pei S, Zhu Q, Chen F.
    Journal: Pharmazie; 2020 Mar 20; 75(2):94-101. PubMed ID: 32213241.
    Abstract:
    An octahedral Pt (IV) prodrug, Cis-wog, containing a wogonin derivative as a bioactive axial ligand was designed and prepared to suppress DDR (DNA damage repair)-related proteins. In vitro biological studies indicated that a Pt (IV) prodrug with axially functional groups (Cis-wog) showed cytotoxicity superior to cisplatin and reversed its resistance against two pairs of cisplatin sensitive and resistant cell lines. Further mechanistic research revealed that the powerful antitumor activity of Cis-wog resulted from its suppression of JWA and its multi-interaction with XRCC1 to repair DNA single strand breaks (SSBs) caused by the introduction of wogonin. It is concluded that Cis-wog is a promising cytotoxic agent, which could be used for enhancing the antitumor activity of its corresponding Pt(II)-based drugs and reversing cisplatin resistance via decaying JWA-mediated SSBs repair pathways and inducing apoptosis.
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