1160844-43-8Relevant articles and documents
Synthesis, Characterization and in vitro Studies of a Cathepsin B-Cleavable Prodrug of the VEGFR Inhibitor Sunitinib
Karnthaler-Benbakka, Claudia,Koblmüller, Bettina,Mathuber, Marlene,Holste, Katharina,Berger, Walter,Heffeter, Petra,Kowol, Christian R.,Keppler, Bernhard K.
, (2019/01/04)
Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small-molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B-cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non-cathepsin B-cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B-expressing cell lines Caki-1 and RU-MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B-cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.
CONJUGATES OF A POLYMER, A BISPHOSPHONATE AND AN ANTI-ANGIOGENESIS AGENT AND USES THEREOF IN THE TREATMENT AND MONITORING OF BONE RELATED DISEASES
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Paragraph 0397-0400, (2016/01/26)
Conjugates of polymers or copolymers having attached thereto an anti-angiogenesis agent and a bisphosphonate bone targeting agent, and processes of preparing same, are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in
Conjugates of a novel 7-substituted camptothecin with RGD-peptides as αvβ3 integrin ligands: An approach to tumor-targeted therapy
Dal Pozzo, Alma,Esposito, Emiliano,Ni, Minghong,Muzi, Laura,Pisano, Claudio,Bucci, Federica,Vesci, Loredana,Castorina, Massimo,Penco, Sergio
scheme or table, p. 1956 - 1967 (2011/08/21)
Eight conjugates of a novel camptothecin derivative (Namitecan, NMT) with RGD peptides have been synthesized and biologically evaluated. This study focused on factors that optimize the drug linkage to the transport vector. The different linkages investigated consist of heterofunctional glycol fragments and a lysosomally cleavable peptide. The linkage length and conformation were systematically modified with the purpose to understand their effect on receptor affinity, systemic stability, cytotoxicity, and solubility of the corresponding conjugates. Among the new conjugates prepared, C6 and C7 showed high receptor affinity and tumor cell adhesion, acceptable stability in murine blood, and high cytotoxic activity (IC50 = 8 nM). The rationale, synthetic strategy, and preliminary biological results will be presented.