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Title: Development of the First Covalent Monopolar Spindle Kinase 1 (MPS1/TTK) Inhibitor

Journal Article · · J. Med. Chem.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
DOE - Office Of Science; National Institutes of Health (NIH)
OSTI ID:
1847130
Journal Information:
J. Med. Chem., Vol. 65, Issue (4)
Country of Publication:
United States
Language:
ENGLISH

References (75)

Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling journal September 2013
Phosphodependent Recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 Kinase Maintains the Spindle Checkpoint journal May 2012
MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components journal June 2012
Mps1 Phosphorylates Borealin to Control Aurora B Activity and Chromosome Alignment journal January 2008
Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs journal August 2013
High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells journal March 2011
Selective Inhibition of Pancreatic Ductal Adenocarcinoma Cell Growth by the Mitotic MPS1 Kinase Inhibitor NMS-P715 journal November 2013
Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores journal June 2008
A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers journal August 2006
Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma journal July 2020
Targeting the Mitotic Checkpoint to Kill Tumor Cells journal December 2010
Characterization of novel MPS1 inhibitors with preclinical anticancer activity journal August 2013
Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase journal April 2020
Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d ]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N 2 -(2-Ethoxy-4-(4-methyl-4 H -1,2,4-triazol-3-yl)phenyl)-6-methyl- N 8 -neopentylpyrido[3,4- d ]pyrimidine-2,8-diamine (BOS172722) journal September 2018
Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer journal March 2017
Kinase Drug Discovery – What’s Next in the Field? journal December 2012
Drug–target residence time and its implications for lead optimization journal August 2006
Binding Kinetics Survey of the Drugged Kinome journal October 2018
Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity journal July 2017
Pharmacokinetics and the drug–target residence time concept journal August 2013
The resurgence of covalent drugs journal April 2011
Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks journal June 2012
The Cysteinome of Protein Kinases as a Target in Drug Development journal February 2018
Advances in covalent kinase inhibitors journal January 2020
Chemical Probes for Understudied Kinases: Challenges and Opportunities journal September 2021
Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs) journal March 2021
Mobocertinib: First Approval journal October 2021
Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology journal December 2018
Covalent inhibitors: back on track? journal August 2020
First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway journal March 2015
First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma journal October 2019
H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma journal December 2017
FGF401, A First-In-Class Highly Selective and Potent FGFR4 Inhibitor for the Treatment of FGF19-Driven Hepatocellular Cancer journal August 2019
Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2) journal October 2021
Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase journal December 2010
Molecular design and anticancer activities of small-molecule monopolar spindle 1 inhibitors: A Medicinal chemistry perspective journal August 2019
Pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors journal February 2021
Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function journal April 2010
Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model journal October 2015
Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction journal December 1973
Mechanism-Based Inhibition: Deriving K I and k inact Directly from Time-Dependent IC 50 Values journal August 2009
Covalent inhibitors design and discovery journal September 2017
Rapidly distinguishing reversible and irreversible CYP450 inhibitors by using fluorometric kinetic analyses journal December 2002
Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance journal December 2013
Systematic Study of the Glutathione Reactivity of N -Phenylacrylamides: 2. Effects of Acrylamide Substitution journal September 2020
Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry journal March 2021
Target engagement and drug residence time can be observed in living cells with BRET journal December 2015
Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1–C-Mad2 core complex journal July 2010
Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity journal February 2016
A quantitative analysis of kinase inhibitor selectivity journal January 2008
The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases journal October 2020
Death-associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes journal June 2018
DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia journal October 2020
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity journal October 2011
Hallmarks of Cancer: The Next Generation journal March 2011
The MPS1 Family of Protein Kinases journal July 2012
Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK1/2 Inhibitor for Treatment of Triple-Negative Breast Cancer with a Compromised G 1 –S Checkpoint journal June 2018
TTK Inhibitors as a Targeted Therapy for CTNNB1 ( β -catenin) Mutant Cancers journal July 2017
TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination journal December 2019
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries journal February 2021
Mps1 kinase regulates tumor cell viability via its novel role in mitochondria journal July 2016
Mitotic checkpoint kinase Mps1/TTK predicts prognosis of colon cancer patients and regulates tumor proliferation and differentiation via PKCα/ERK1/2 and PI3K/Akt pathway journal November 2019
TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability: Effect of Mps1 inhibitor on hepatocellular carcinoma cells journal April 2017
Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer journal September 2016
Unmasking senescence: context-dependent effects of SASP in cancer journal June 2019
Systematic Study of the Glutathione (GSH) Reactivity of N -Arylacrylamides: 1. Effects of Aryl Substitution journal November 2015
High-throughput production of human proteins for crystallization: The SGC experience journal October 2010
XDS journal January 2010
Overview of the CCP 4 suite and current developments journal March 2011
Features and development of Coot journal March 2010
MolProbity : all-atom structure validation for macromolecular crystallography journal December 2009
Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement journal February 2018
Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2 journal May 2021
Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors journal January 2019
Discovery of a Novel Class of Covalent Dual Inhibitors Targeting the Protein Kinases BMX and BTK journal December 2020

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