Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases

Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex

2005 • 5,837 citations

PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

1997 • 4,753 citations

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

2007 • 4,320 citations

High Frequency of Mutations of the PIK3CA Gene in Human Cancers

2004 • 3,304 citations

A synthetic inhibitor of the mitogen-activated protein kinase cascade.

1995 • 2,723 citations

A quantitative analysis of kinase inhibitor selectivity

2008 • 2,334 citations

Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor

1996 • 1,946 citations

Ras, PI(3)K and mTOR signalling controls tumour cell growth

2006 • 1,934 citations

Skepinone-L, a Novel Potent and Highly Selective Inhibitor of p38 MAP Kinase, Effectively Impairs Platelet Activation and Thrombus Formation

2013 • 1,823 citations

Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase

2000 • 1,770 citations

Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor

2002 • 1,717 citations

Molecular Determinants of the Response of Glioblastomas to EGFR Kinase Inhibitors

2005 • 1,418 citations

A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia

1982 • 1,385 citations

Tyrosine Kinases as Targets for Cancer Therapy

2005 • 1,365 citations

Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and Staurosporine

2000 • 1,121 citations

A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling

2006 • 1,119 citations

Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity

2008 • 1,099 citations

Rational design of inhibitors that bind to inactive kinase conformations

2006 • 1,013 citations

Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3

2007 • 941 citations

Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies

2007 • 910 citations

Mutant PIK3CA promotes cell growth and invasion of human cancer cells

2005 • 873 citations

Phase II Trial of Sorafenib in Advanced Thyroid Cancer

2008 • 673 citations

Features of Selective Kinase Inhibitors

2005 • 625 citations

A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma

2006 • 587 citations

Frequent Co‐Alterations of TP53, p16/CDKN2A, p14^ARF, PTEN Tumor Suppressor Genes in Human Glioma Cell Lines.

1999 • 539 citations

Oncogenic Mutations of PIK3CA in Human Cancers

2004 • 502 citations

Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors

2005 • 496 citations

Angiogenesis selectively requires the p110α isoform of PI3K to control endothelial cell migration

2008 • 487 citations

Structural insights into phosphoinositide 3-kinase catalysis and signalling

1999 • 478 citations

Epidermal Growth Factor Receptor, Protein Kinase B/Akt, and Glioma Response to Erlotinib

2005 • 468 citations

BAY 43-9006 Inhibition of Oncogenic RET Mutants

2006 • 466 citations

Can we rationally design promiscuous drugs?

2006 • 461 citations

Crystal Structure of Hck in Complex with a Src Family–Selective Tyrosine Kinase Inhibitor

1999 • 428 citations

Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor

1998 • 414 citations

Mechanisms of drug inhibition of signalling molecules

2006 • 295 citations

Structural Evolution of the Protein Kinase–Like Superfamily

2005 • 253 citations

Structural basis for selective inhibition of Src family kinases by PP1

1999 • 249 citations

Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs

2004 • 245 citations

Mammalian Target of Rapamycin Inhibition Promotes Response to Epidermal Growth Factor Receptor Kinase Inhibitors in PTEN-Deficient and PTEN-Intact Glioblastoma Cells

2006 • 235 citations

Wortmannin, a Widely Used Phosphoinositide 3-Kinase Inhibitor, also Potently Inhibits Mammalian Polo-like Kinase

2005 • 201 citations

A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN-Mutant Glioma

2007 • 190 citations

Chemically targeting the PI3K family

2007 • 127 citations

Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway

2008 • 87 citations

Point Mutation of the RetProto-oncogene in the TT Human Medullary Thyroid Carcinoma Cell Line

1995 • 76 citations

Combinatorial efficacy achieved through two-point blockade within a signaling pathway-a chemical genetic approach.

2003 • 75 citations

Mixing cocktails

2007 • 55 citations