What question did this study set out to answer?

To characterize the kinase inhibitory profile, cellular mechanism of action, and in vivo antitumor efficacy of the novel indolinone derivative BIBF 1120.

June 15, 2008Cancer ResearchOpen Access

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy

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To characterize the kinase inhibitory profile, cellular mechanism of action, and in vivo antitumor efficacy of the novel indolinone derivative BIBF 1120.
Assessed enzymatic inhibition across VEGFR, PDGFR, and FGFR kinases and measured downstream MAPK and Akt signaling, proliferation, and apoptosis in endothelial cells, pericytes, and smooth muscle cells.
Administered oral BIBF 1120 at 25–100 mg/kg daily in human tumor xenografts in nude mice and a syngeneic rat model, assessing tumor perfusion via MRI and evaluating vessel density.
Inhibited VEGFR, PDGFR, and FGFR kinase activity with IC50 values of 20–100 nmol/L and suppressed endothelial, pericyte, and smooth muscle cell proliferation with EC50 values of 10–80 nmol/L.
Maintained cellular pathway inhibition for up to 32 hours following a 1-hour exposure in vitro, demonstrating sustained receptor blockade despite rapid in vivo methylester cleavage.
Reduced tumor perfusion after 3 days and decreased vessel density and integrity after 5 days, yielding pronounced tumor growth inhibition across all tested models with once-daily oral dosing.

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Implication

Preclinical study reveals potent antitumor activity and sustained receptor blockade with BIBF 1120 in rodent tumor models, highlighting therapeutic promise for multi-target kinase inhibition.

Cite This Study

Hilberg et al. (2008) studied this question.

synapsesocial.com/papers/69dcc3f67873f5f05b133c3e https://doi.org/10.1158/0008-5472.can-07-6307

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Implication

Preclinical study reveals potent antitumor activity and sustained receptor blockade with BIBF 1120 in rodent tumor models, highlighting therapeutic promise for multi-target kinase inhibition.

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy

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Cite This Study

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy

Key Points

Discussion

Implication

Cite This Study

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