Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and vascular disrupting agent

Drug Design, Development and Therapy
Linda RickardsonStefan Rehnmark

Abstract

Overall, ~65% of patients diagnosed with advanced ovarian cancer (OC) will relapse after primary surgery and adjuvant first-line platinum- and taxane-based chemotherapy. Significant improvements in the treatment of OC are expected from the development of novel compounds having combined cytotoxic and antiangiogenic properties that make them effective on refractory tumors. Permeability of NOV202 was determined with Caco-2 monolayer assay. The compound's pharmacokinetic profile and plasma:brain distribution were assessed in male C57Bl/6 mice. The compound's impacts on tubulin, microtubules and cell cycle were investigated by using in vitro tubulin polymerization assay, cell-based immunofluorescence and live cell microscopy. The IC50concentrations of NOV202 were assessed in a panel of eight cancer cell lines. Impact of the compound on vascular tube formation was determined using the StemKit and Chick chorioallantoic membrane assays. The in vivo efficacy of the compound was analyzed with an OC xenograft mouse model. NOV202 was found to suppress cancer cell proliferation at low nanomolar concentrations (IC502.3-12.0 nM) and showed equal efficacy between OC cell line A2780 (IC502.4 nM) and its multidrug-resistant subline A2780/Adr (IC...Continue Reading

Citations

Oct 16, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Bahar Yetkin-ArikCornelis J F van Noorden
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li LiuRalph P Mason

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Methods Mentioned

BETA
xenograft

Software Mentioned

GraphPadPrism
GraphPad
NOV202
IncuCyte
Metamorph

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