Related Experiment Video

Updated: Jun 23, 2026

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

Dorothea Rudolph1, Martin Steegmaier, Matthias Hoffmann

  • 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 23, 2009
PubMed
Abstract

Insights

BI 6727, a novel Polo-like kinase 1 inhibitor, shows potent and selective antimitotic activity. This agent demonstrates promising antitumor effects in preclinical models, including taxane-resistant cancers, and allows flexible dosing via oral or IV routes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Antimitotic chemotherapy is crucial for treating advanced cancers.
  • Existing tubulin-binding agents have limitations in selectivity.
  • Polo-like kinase 1 (PLK1) is a key mitotic regulator and a target for novel cancer therapies.

Purpose of the Study:

  • To identify novel, selective antimitotic agents targeting Polo-like kinase 1 (PLK1).
  • To profile and characterize a new clinical candidate, BI 6727, for its potential in oncology.

Main Methods:

  • Generation and profiling of Polo-like kinase 1 (PLK1) inhibitors.
  • In vitro enzyme and cellular assays to determine potency and selectivity (IC50, EC50).
  • Pharmacokinetic studies in mice and rats to assess distribution and half-life.
  • In vivo efficacy studies in various cancer models, including taxane-resistant models.
  • Evaluation of both intravenous (IV) and oral formulations.

Main Results:

  • BI 6727 is a potent and selective dihydropteridinone inhibitor of PLK1 (enzyme IC50 = 0.87 nmol/L, EC50 = 11-37 nmol/L).
  • BI 6727 exhibits favorable pharmacokinetics with sustained tumor exposure, high volume of distribution, and long half-life in rodents.
  • The compound allows for flexible dosing schedules with both IV and oral administration.
  • BI 6727 demonstrated significant antitumor activity across multiple cancer models, including a taxane-resistant colorectal cancer model.

Conclusions:

  • BI 6727 shows promise as a tailored antimitotic agent targeting PLK1.
  • Its distinct properties, including potent activity, favorable pharmacokinetics, and flexible administration, warrant further clinical investigation.
  • Clinical studies of BI 6727 have been initiated.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...