Mitosis as an anti-cancer drug target

A phase I study of MK-5108, an oral aurora A kinase inhibitor, in both monotherapy and in combination with docetaxel in patients with advanced solid tumors.

(2017) S. E. Minton et al.   JOURNAL OF CLINICAL ONCOLOGY

Killing cells by targeting mitosis

(2012) E Manchado et al.   CELL DEATH AND DIFFERENTIATION

Inhibitors Targeting Mitosis: Tales of How Great Drugs against a Promising Target Were Brought Down by a Flawed Rationale

(2012) E. Komlodi-Pasztor et al.   CLINICAL CANCER RESEARCH

A Phase I Open-Label Dose-Escalation Study of Intravenous BI 2536 Together With Pemetrexed in Previously Treated Patients With Non–Small-Cell Lung Cancer

(2012) Peter M. Ellis et al.   Clinical Lung Cancer

Losing balance: the origin and impact of aneuploidy in cancer

(2012) Andrew J Holland et al.   EMBO REPORTS

ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer

(2012) Ursula A. Matulonis et al.   EUROPEAN JOURNAL OF CANCER

HDAC modulation and cell death in the clinic

(2012) Carmela Dell'Aversana et al.   EXPERIMENTAL CELL RESEARCH

ENMD-2076 for hematological malignancies

(2012) Jonathan How et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

(2012) Ursula A. Matulonis et al.   GYNECOLOGIC ONCOLOGY

CENP-E–dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint

(2012) Yige Guo et al.   JOURNAL OF CELL BIOLOGY

Mitosis-targeted anti-cancer therapies: where they stand

(2012) K-S Chan et al.   Cell Death & Disease

Selective Aurora Kinase Inhibitors Identified Using a Taxol-Induced Checkpoint Sensitivity Screen

(2011) Nicholas Kwiatkowski et al.   ACS Chemical Biology

NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor

(2011) Italo Beria et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

(2011) B. Lowenberg et al.   BLOOD

Aurora B kinase inhibitor AZD1152: determinants of action and ability to enhance chemotherapeutics effectiveness in pancreatic and colon cancer

(2011) A Azzariti et al.   BRITISH JOURNAL OF CANCER

First-time-in-human study of GSK923295, a novel antimitotic inhibitor of centromere-associated protein E (CENP-E), in patients with refractory cancer

(2011) Vincent Chung et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Chromosomal Instability Confers Intrinsic Multidrug Resistance

(2011) A. J. X. Lee et al.   CANCER RESEARCH

Identification of Aneuploidy-Selective Antiproliferation Compounds

(2011) Yun-Chi Tang et al.   CELL

The Ndc80 complex: integrating the kinetochore's many movements

(2011) John Tooley et al.   CHROMOSOME RESEARCH

Phase I Study of GSK461364, a Specific and Competitive Polo-like Kinase 1 Inhibitor, in Patients with Advanced Solid Malignancies

(2011) D. Olmos et al.   CLINICAL CANCER RESEARCH

Chromosomal Instability Substantiates Poor Prognosis in Patients with Diffuse Large B-cell Lymphoma

(2011) S. F. Bakhoum et al.   CLINICAL CANCER RESEARCH

PLK1 as an oncology target: current status and future potential

(2011) Campbell McInnes et al.   DRUG DISCOVERY TODAY

A phase I, dose-escalation study of the novel Polo-like kinase inhibitor volasertib (BI 6727) in patients with advanced solid tumours

(2011) Patrick Schöffski et al.   EUROPEAN JOURNAL OF CANCER

From cell biology to therapy: ENMD-2076 in the treatment of multiple myeloma

(2011) Shuhong Zhang et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Aurora kinase inhibitor patents and agents in clinical testing: an update (2009 – 10)

(2011) Chun Hei Antonio Cheung et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

The Ndc80 complex uses a tripartite attachment point to couple microtubule depolymerization to chromosome movement

(2011) John G. Tooley et al.   MOLECULAR BIOLOGY OF THE CELL

Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint

(2011) Randy Wei et al.   MOLECULAR BIOLOGY OF THE CELL

The proliferation rate paradox in antimitotic chemotherapy

(2011) Timothy J. Mitchison   MOLECULAR BIOLOGY OF THE CELL

Characterization of the Cellular and Antitumor Effects of MPI-0479605, a Small-Molecule Inhibitor of the Mitotic Kinase Mps1

(2011) K. D. Tardif et al.   MOLECULAR CANCER THERAPEUTICS

Spindle Poisons and Cell Fate: A Tale of Two Pathways

(2011) D. R. Matson et al.   MOLECULAR INTERVENTIONS

Centrosome clustering and chromosomal (in)stability: A matter of life and death

(2011) Alwin Krämer et al.   Molecular Oncology

SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction

(2011) Hiroyuki Inuzuka et al.   NATURE

Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

(2011) Ingrid E. Wertz et al.   NATURE

Mitosis as an anti-cancer target

(2011) A Janssen et al.   ONCOGENE

Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors

(2010) D. S. Boss et al.   ANNALS OF ONCOLOGY

Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state

(2010) J. den Hollander et al.   BLOOD

Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors

(2010) E. Claire Dees et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A first in human study of SB-743921, a kinesin spindle protein inhibitor, to determine pharmacokinetics, biologic effects and establish a recommended phase II dose

(2010) Kyle D. Holen et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase

(2010) A. Chakravarty et al.   CANCER RESEARCH

Molecular Causes for BUBR1 Dysfunction in the Human Cancer Predisposition Syndrome Mosaic Variegated Aneuploidy

(2010) Saskia J.E. Suijkerbuijk et al.   CANCER RESEARCH

Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase

(2010) R. Colombo et al.   CANCER RESEARCH

Aurora Kinases and Protein Phosphatase 1 Mediate Chromosome Congression through Regulation of CENP-E

(2010) Yumi Kim et al.   CELL

Probing CENP-E function in chromosome dynamics using small molecule inhibitor syntelin

(2010) Xia Ding et al.   CELL RESEARCH

Activity of the Kinesin Spindle Protein Inhibitor Ispinesib (SB-715992) in Models of Breast Cancer

(2010) J. W. Purcell et al.   CLINICAL CANCER RESEARCH

Prolonged Prometaphase Blocks Daughter Cell Proliferation Despite Normal Completion of Mitosis

(2010) Yumi Uetake et al.   CURRENT BIOLOGY

Phosphorylation of Mcl-1 by CDK1–cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest

(2010) Margaret E Harley et al.   EMBO JOURNAL

A chemical tool box defines mitotic and interphase roles for Mps1 kinase

(2010) Weijie Lan et al.   JOURNAL OF CELL BIOLOGY

Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine

(2010) Stefano Santaguida et al.   JOURNAL OF CELL BIOLOGY

Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1–C-Mad2 core complex

(2010) Laura Hewitt et al.   JOURNAL OF CELL BIOLOGY

Mitotic drug targets

(2010) Phillip Kaestner et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Discovery ofN-Phenyl-4-(thiazol-5-yl)pyrimidin-2-amine Aurora Kinase Inhibitors

(2010) Shudong Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Efficacy and Safety of BI 2536, a Novel Plk-1 Inhibitor, in Patients with Stage IIIB/IV Non-small Cell Lung Cancer Who Had Relapsed after, or Failed, Chemotherapy: Results from an Open-Label, Randomized Phase II Clinical Trial

(2010) Martin Sebastian et al.   Journal of Thoracic Oncology

PF-03814735, an Orally Bioavailable Small Molecule Aurora Kinase Inhibitor for Cancer Therapy

(2010) Jitesh P. Jani et al.   MOLECULAR CANCER THERAPEUTICS

MK-5108, a Highly Selective Aurora-A Kinase Inhibitor, Shows Antitumor Activity Alone and in Combination with Docetaxel

(2010) T. Shimomura et al.   MOLECULAR CANCER THERAPEUTICS

Sensitivity of Cancer Cells to Plk1 Inhibitor GSK461364A Is Associated with Loss of p53 Function and Chromosome Instability

(2010) Y. Degenhardt et al.   MOLECULAR CANCER THERAPEUTICS

Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal

(2010) Rocio Sotillo et al.   NATURE

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function

(2010) Nicholas Kwiatkowski et al.   Nature Chemical Biology

A pediatric phase I trial and pharmacokinetic study of ispinesib: A Children's Oncology Group phase I consortium study

(2010) Abdul-Kader Souid et al.   PEDIATRIC BLOOD & CANCER

Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase

(2010) D. Yang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Antitumor activity of an allosteric inhibitor of centromere-associated protein-E

(2010) K. W. Wood et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutational Analysis of TTK Gene in Gastric and Colorectal Cancers with Microsatellite Instability

(2010) Chang Hyeok Ahn et al.   Cancer Research and Treatment

Mutations in the human kinesin Eg5 that confer resistance to monastrol and S-trityl- l -cysteine in tumor derived cell lines

(2009) Sergey Tcherniuk et al.   BIOCHEMICAL PHARMACOLOGY

Evidence that Mitotic Exit Is a Better Cancer Therapeutic Target Than Spindle Assembly

(2009) Hsiao-Chun Huang et al.   CANCER CELL

Distinct Concentration-Dependent Effects of the Polo-like Kinase 1-Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis

(2009) A. G. Gilmartin et al.   CANCER RESEARCH

Pharmacologic Abrogation of the Mitotic Spindle Checkpoint by an Indolocarbazole Discovered by Cellular Screening Efficiently Kills Cancer Cells

(2009) A. Stolz et al.   CANCER RESEARCH

Dietary flavonoid fisetin induces a forced exit from mitosis by targeting the mitotic spindle checkpoint

(2009) Anna-Leena Salmela et al.   CARCINOGENESIS

A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene

(2009) Ji Luo et al.   CELL

BI 6727, A Polo-like Kinase Inhibitor with Improved Pharmacokinetic Profile and Broad Antitumor Activity

(2009) D. Rudolph et al.   CLINICAL CANCER RESEARCH

Mechanisms of Drug-Induced Mitotic Catastrophe in Cancer Cells

(2009) Jose Portugal et al.   CURRENT PHARMACEUTICAL DESIGN

Short and long-term tumor cell responses to Aurora kinase inhibitors

(2009) Megan R. Dreier et al.   EXPERIMENTAL CELL RESEARCH

Role of prolonged mitotic checkpoint activation in the formation and treatment of cancer

(2009) W Brian Dalton et al.   Future Oncology

Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen

(2009) John McLaughlin et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

How do anti-mitotic drugs kill cancer cells?

(2009) K. E. Gascoigne et al.   JOURNAL OF CELL SCIENCE

Chromosomal instability correlates with poor outcome in patients with myelodysplastic syndromes irrespectively of the cytogenetic risk group

(2009) Christoph E. Heilig et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

The selective Aurora B kinase inhibitor AZD1152 as a novel treatment for hepatocellular carcinoma

(2009) Arihiro Aihara et al.   JOURNAL OF HEPATOLOGY

Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues

(2009) Xiao-Long Qiu et al.   JOURNAL OF MEDICINAL CHEMISTRY

TTK/hMps1 Mediates the p53-Dependent Postmitotic Checkpoint by Phosphorylating p53 at Thr18

(2009) Y.-F. Huang et al.   MOLECULAR AND CELLULAR BIOLOGY

Cyclin-Dependent Kinase 1-Mediated Bcl-xL/Bcl-2 Phosphorylation Acts as a Functional Link Coupling Mitotic Arrest and Apoptosis

(2009) D. T. Terrano et al.   MOLECULAR AND CELLULAR BIOLOGY

Aurora B Kinase Regulates the Postmitotic Endoreduplication Checkpoint via Phosphorylation of the Retinoblastoma Protein at Serine 780

(2009) Jayasree S. Nair et al.   MOLECULAR BIOLOGY OF THE CELL

UA62784, a novel inhibitor of centromere protein E kinesin-like protein

(2009) M. C. Henderson et al.   MOLECULAR CANCER THERAPEUTICS

Determinants for the efficiency of anticancer drugs targeting either Aurora-A or Aurora-B kinases in human colon carcinoma cells

(2009) P. Kaestner et al.   MOLECULAR CANCER THERAPEUTICS

Cell cycle kinases as therapeutic targets for cancer

(2009) Silvia Lapenna et al.   NATURE REVIEWS DRUG DISCOVERY

Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells

(2009) Aniek Janssen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chromosomal instability determines taxane response

(2009) C. Swanton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Getting down to the phosphorylated ‘nuts and bolts’ of spindle checkpoint signalling

(2009) Judith Zich et al.   TRENDS IN BIOCHEMICAL SCIENCES

Is the focus moving toward a combination of targeted drugs?

(2008) Steven Grant   BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY

An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner

(2008) Eun Joo Noh et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I

(2008) A. Gontarewicz et al.   BLOOD

A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours

(2008) S P Blagden et al.   BRITISH JOURNAL OF CANCER

Farnesyltransferase inhibitors and their potential role in therapy for myelodysplastic syndromes and acute myeloid leukaemia

(2008) Thorsten Braun et al.   BRITISH JOURNAL OF HAEMATOLOGY

The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma

(2008) Robert P. Evans et al.   BRITISH JOURNAL OF HAEMATOLOGY

The Aneuploidy Paradox in Cell Growth and Tumorigenesis

(2008) Beth A. Weaver et al.   CANCER CELL

Cancer Cells Display Profound Intra- and Interline Variation following Prolonged Exposure to Antimitotic Drugs

(2008) Karen E. Gascoigne et al.   CANCER CELL

Farnesyl Transferase Inhibitors

(2008) Tianhong Li et al.   CANCER INVESTIGATION

Histone deacetylase inhibitors and genomic instability

(2008) Grégory Eot-Houllier et al.   CANCER LETTERS

Small Molecule Targeting the Hec1/Nek2 Mitotic Pathway Suppresses Tumor Cell Growth in Culture and in Animal

(2008) G. Wu et al.   CANCER RESEARCH

Cell Type Variation in Responses to Antimitotic Drugs that Target Microtubules and Kinesin-5

(2008) J. Shi et al.   CANCER RESEARCH

Mps1 Phosphorylates Borealin to Control Aurora B Activity and Chromosome Alignment

(2008) Nannette Jelluma et al.   CELL

Inhibition of Polo-like Kinase 1 by Blocking Polo-Box Domain-Dependent Protein-Protein Interactions

(2008) Wolfgang Reindl et al.   CHEMISTRY & BIOLOGY

Centromere-Associated Protein E: A Motor That Puts the Brakes on the Mitotic Checkpoint

(2008) K. W. Wood et al.   CLINICAL CANCER RESEARCH

A University of Chicago Consortium Phase II Trial of SB-715992 in Advanced Renal Cell Cancer

(2008) Richard T. Lee et al.   Clinical Genitourinary Cancer

Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts

(2008) E. Walsby et al.   HAEMATOLOGICA

Crystal Structure of the Catalytic Domain of the Mitotic Checkpoint Kinase Mps1 in Complex with SP600125

(2008) Matthew L. H. Chu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Deficiency in Chromosome Congression by the Inhibition of Plk1 Polo Box Domain-dependent Recognition

(2008) Nobumoto Watanabe et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores

(2008) Anthony Tighe et al.   JOURNAL OF CELL BIOLOGY

Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit

(2008) Haomin Huang et al.   JOURNAL OF CELL BIOLOGY

Examining the link between chromosomal instability and aneuploidy in human cells

(2008) Sarah L. Thompson et al.   JOURNAL OF CELL BIOLOGY

Structural and mechanistic insights into Mps1 kinase activation

(2008) Wei Wang et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Phase I Dose Escalation and Pharmacokinetic Study of BI 2536, a Novel Polo-Like Kinase 1 Inhibitor, in Patients With Advanced Solid Tumors

(2008) Klaus Mross et al.   JOURNAL OF CLINICAL ONCOLOGY

Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from Korean patients

(2008) Chang-Min Choi et al.   LUNG CANCER

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

(2008) A. M. D'Alise et al.   MOLECULAR CANCER THERAPEUTICS

Phosphorylation Relieves Autoinhibition of the Kinetochore Motor Cenp-E

(2008) Julien Espeut et al.   MOLECULAR CELL

The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

(2008) J Du et al.   ONCOGENE

Chromosomal Instability by Inefficient Mps1 Auto-Activation Due to a Weakened Mitotic Checkpoint and Lagging Chromosomes

(2008) Nannette Jelluma et al.   PLoS One

Histone Deacetylation

(2008) Anas Al-Janadi et al.   Drugs in research & development

The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and cancer (U2OS, HeLa) cells

(2008) Daniela A. Brito et al.   CELL MOTILITY AND THE CYTOSKELETON

Discovery and biochemical characterization of selective ATP competitive inhibitors of the human mitotic kinesin KSP

(2007) Keith W. Rickert et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Survival of aneuploid, micronucleated and/or polyploid cells: Crosstalk between ploidy control and apoptosis

(2007) Ilse Decordier et al.   MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS