Clinical cancer research : an official journal of the American Association for Cancer ResearchApr 23, 2009

BI 6727, a drug that blocks cell division with better body processing and wide cancer-fighting effects

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

BI 6727 demonstrates high potency with an enzyme IC(50) of 0.87 nmol/L and shows marked antitumor activity in various cancer models.

BI 6727 exhibits a pharmacokinetic profile that favors sustained exposure in tumor tissues, with a high volume of distribution and a long terminal half-life in mice (46 hours) and rats (54 hours).
The compound allows for both intravenous and oral formulations, providing flexibility in dosing schedules.
Significant antitumor activity has been observed in models of taxane-resistant colorectal cancer.
The total weekly dose is crucial for efficacy, supporting diverse and well-tolerated dosing regimens.
Clinical studies to further evaluate BI 6727 as an antimitotic agent have been initiated.

Simplified

PURPOSE: Antimitotic chemotherapy remains a cornerstone of multimodality treatment for locally advanced and metastatic cancers. To identify novel mitosis-specific agents with higher selectivity than approved tubulin-binding agents (taxanes, Vinca alkaloids), we have generated inhibitors of Polo-like kinase 1, a target that functions predominantly in mitosis.

EXPERIMENTAL DESIGN: The first compound in this series, suitable for i.v. administration, has entered clinical development. To fully explore the potential of Polo-like kinase 1 inhibition in oncology, we have profiled additional compounds and now describe a novel clinical candidate.

RESULTS: BI 6727 is a highly potent (enzyme IC(50) = 0.87 nmol/L, EC(50) = 11-37 nmol/L on a panel of cancer cell lines) and selective dihydropteridinone with distinct properties. First, BI 6727 has a pharmacokinetic profile favoring sustained exposure of tumor tissues with a high volume of distribution and a long terminal half-life in mice (V(ss) = 7.6 L/kg, t(1/2) = 46 h) and rats (V(ss) = 22 L/kg, t(1/2) = 54 h). Second, BI 6727 has physicochemical and pharmacokinetic properties that allow in vivo testing of i.v. as well as oral formulations, adding flexibility to dosing schedules. Finally, BI 6727 shows marked antitumor activity in multiple cancer models, including a model of taxane-resistant colorectal cancer. With oral and i.v. routes of administration, the total weekly dose of BI 6727 is most relevant for efficacy, supporting the use of a variety of well-tolerated dosing schedules.

CONCLUSION: These findings warrant further investigation of BI 6727 as a tailored antimitotic agent; clinical studies have been initiated.

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BI 6727, a drug that blocks cell division with better body processing and wide cancer-fighting effects

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