Targeting the cancer kinome through polypharmacology.

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Published in Nat Rev Cancer on February 01, 2010

Authors

Zachary A Knight1, Henry Lin, Kevan M Shokat

Author Affiliations

1: Zachary A. Knight is at The Rockefeller University, New York, New York 10065, USA.

Associated clinical trials:

Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid Cancer | NCT02363647

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Complementary detection of prostate-specific antigen using In2O3 nanowires and carbon nanotubes. J Am Chem Soc (2005) 1.97

A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci U S A (2007) 1.97

A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition. Biochem J (2008) 1.96

Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain. Proc Natl Acad Sci U S A (2003) 1.93

The cyclin-dependent kinase (CDK) family member PNQALRE/CCRK supports cell proliferation but has no intrinsic CDK-activating kinase (CAK) activity. Cell Cycle (2006) 1.90

Hierarchical modularity and the evolution of genetic interactomes across species. Mol Cell (2012) 1.88

A neo-substrate that amplifies catalytic activity of parkinson's-disease-related kinase PINK1. Cell (2013) 1.84

Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol (2003) 1.82

Phosphorylation of the transcription elongation factor Spt5 by yeast Bur1 kinase stimulates recruitment of the PAF complex. Mol Cell Biol (2009) 1.82

The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling. Annu Rev Biochem (2011) 1.80

Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLoS Biol (2009) 1.78

Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold. Bioorg Med Chem (2004) 1.77

Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha. Mol Biol Cell (2007) 1.77

Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat Struct Mol Biol (2012) 1.74

The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nat Struct Mol Biol (2008) 1.73

Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell (2009) 1.72

Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis. Proc Natl Acad Sci U S A (2007) 1.71

Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast. Genes Dev (2008) 1.68

Industrial production of recombinant therapeutics in Escherichia coli and its recent advancements. J Ind Microbiol Biotechnol (2012) 1.67

Suppression of p53-dependent senescence by the JNK signal transduction pathway. Proc Natl Acad Sci U S A (2007) 1.67

Bio-orthogonal affinity purification of direct kinase substrates. J Am Chem Soc (2005) 1.67

The protein kinase Kin4 inhibits exit from mitosis in response to spindle position defects. Mol Cell (2005) 1.67

TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol Cell (2009) 1.66

EGFR signals to mTOR through PKC and independently of Akt in glioma. Sci Signal (2009) 1.66

Combining chemical genetics and proteomics to identify protein kinase substrates. Proc Natl Acad Sci U S A (2005) 1.63

Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs. J Biol Chem (2003) 1.60

Phosphospecific proteolysis for mapping sites of protein phosphorylation. Nat Biotechnol (2003) 1.60

Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood (2009) 1.58

Dissecting the Engrailed homeodomain-DNA interaction by phage-displayed shotgun scanning. Chem Biol (2004) 1.56

Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells. J Clin Invest (2008) 1.56

Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Proc Natl Acad Sci U S A (2013) 1.53

Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem (2006) 1.52

The emerging power of chemical genetics. Curr Opin Cell Biol (2002) 1.52

Ultrasonography in community emergency departments in the United States: access to ultrasonography performed by consultants and status of emergency physician-performed ultrasonography. Ann Emerg Med (2005) 1.52

Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation. Mol Cell (2009) 1.51