New approaches to molecular cancer therapeutics

The Hallmarks of Cancer

2000 • 27,569 citations

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

2001 • 16,438 citations

Mutations of the BRAF gene in human cancer

2002 • 10,249 citations

EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

2004 • 9,201 citations

Molecular Properties That Influence the Oral Bioavailability of Drug Candidates

2002 • 6,592 citations

Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

2005 • 6,083 citations

In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

2004 • 4,416 citations

Cancer genes and the pathways they control

2004 • 4,172 citations

Can the pharmaceutical industry reduce attrition rates?

2004 • 3,946 citations

Docking and scoring in virtual screening for drug discovery: methods and applications

2004 • 3,411 citations

An inhibitor of Bcl-2 family proteins induces regression of solid tumours

2005 • 3,292 citations

A census of human cancer genes

2004 • 3,190 citations

The NCI60 human tumour cell line anticancer drug screen

2006 • 2,439 citations

Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer

2006 • 2,149 citations

Protein kinases — the major drug targets of the twenty-first century?

2002 • 2,101 citations

A small molecule–kinase interaction map for clinical kinase inhibitors

2005 • 1,854 citations

Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor

2004 • 1,785 citations

Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors

1999 • 1,640 citations

Molecular mechanisms of drug resistance

2005 • 1,510 citations

Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma

2005 • 1,478 citations

Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug

2002 • 1,349 citations

The specificities of protein kinase inhibitors: an update

2003 • 1,345 citations

BRAF mutation predicts sensitivity to MEK inhibition

2005 • 1,312 citations

Protein Kinase Inhibitors: Insights into Drug Design from Structure

2004 • 1,180 citations

Lessons from natural molecules

2004 • 1,110 citations

The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

2004 • 1,101 citations

A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening

2002 • 1,039 citations

Rational design of inhibitors that bind to inactive kinase conformations

2006 • 1,013 citations

Structural Basis for Inhibition of the Hsp90 Molecular Chaperone by the Antitumor Antibiotics Radicicol and Geldanamycin

1999 • 979 citations

Navigating chemical space for biology and medicine

2004 • 977 citations

Stem Cells and Cancer: Two Faces of Eve

2006 • 909 citations

Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP

1996 • 881 citations

Global mapping of pharmacological space

2006 • 798 citations

Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries

2006 • 784 citations

Fragment-based lead discovery

2004 • 773 citations

Clinical biomarkers in drug discovery and development

2003 • 761 citations

Is There a Difference between Leads and Drugs? A Historical Perspective

2001 • 757 citations

Mechanisms of cutaneous toxicities to EGFR inhibitors

2006 • 724 citations

Potent and selective inhibitors of the proteasome: Dipeptidyl boronic acids

1998 • 674 citations

Natural products in cancer chemotherapy: past, present and future

2002 • 670 citations

Structural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases

2004 • 662 citations

The mighty mouse: genetically engineered mouse models in cancer drug development

2006 • 631 citations

Features of Selective Kinase Inhibitors

2005 • 625 citations

Systematic discovery of multicomponent therapeutics

2003 • 616 citations

Diversity-oriented synthesis: exploring the intersections between chemistry and biology

2005 • 596 citations

Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition

2004 • 588 citations

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

2006 • 587 citations

Systems biology and combination therapy in the quest for clinical efficacy

2006 • 562 citations

Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors

2005 • 496 citations

Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino, 17-Demethoxygeldanamycin in Patients With Advanced Malignancies

2005 • 489 citations

Keynote review: In vitro safety pharmacology profiling: an essential tool for successful drug development

2005 • 377 citations

Nonleadlikeness and leadlikeness in biochemical screening

2003 • 376 citations

Biochemical mechanisms of drug action: what does it take for success?

2004 • 370 citations

Characteristic Physical Properties and Structural Fragments of Marketed Oral Drugs

2003 • 353 citations

Contributions of Human Tumor Xenografts to Anticancer Drug Development

2006 • 345 citations

Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy

2006 • 339 citations

Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing

2006 • 337 citations

A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells

2003 • 326 citations

Drug Insight: histone deacetylase inhibitors—development of the new targeted anticancer agent suberoylanilide hydroxamic acid

2005 • 319 citations

The New Era in Cancer Research

2006 • 298 citations

Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis

2006 • 294 citations

A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells

2001 • 282 citations

Combined Application of Parallel Artificial Membrane Permeability Assay and Caco-2 Permeability Assays in Drug Discovery

2004 • 259 citations

Structure-Activity Relationships in Purine-Based Inhibitor Binding to HSP90 Isoforms

2004 • 255 citations

Cellular Targets of Gefitinib

2005 • 236 citations

Novel, Potent Small-Molecule Inhibitors of the Molecular Chaperone Hsp90 Discovered through Structure-Based Design

2005 • 231 citations

The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

2005 • 221 citations

Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling

2005 • 220 citations

Medicinal chemistry of target family-directed masterkeys

2003 • 208 citations

A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design

2005 • 203 citations

Cancer Biomarkers—An Invitation to the Table

2006 • 199 citations

Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment

2005 • 193 citations

Minimally Invasive Pharmacokinetic and Pharmacodynamic Technologies in Hypothesis-Testing Clinical Trials of Innovative Therapies

2006 • 190 citations

An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors

2006 • 186 citations

Tools for kinetic modeling of biochemical networks

2006 • 183 citations

Identification of Novel p38α MAP Kinase Inhibitors Using Fragment-Based Lead Generation

2004 • 178 citations

Opportunities and challenges in the development of kinase inhibitor therapy for cancer

2003 • 171 citations

Improving the decision-making process in the structural modification of drug candidates: enhancing metabolic stability

2004 • 171 citations

Pharmacokinetic-Pharmacodynamic Relationships for the Heat Shock Protein 90 Molecular Chaperone Inhibitor 17-Allylamino, 17-Demethoxygeldanamycin in Human Ovarian Cancer Xenograft Models

2005 • 166 citations

Influence of Molecular Flexibility and Polar Surface Area Metrics on Oral Bioavailability in the Rat

2004 • 159 citations

Validating cancer drug targets

2006 • 154 citations

How Much Gets there and What Does it Do?: The Need for Better Pharmacokinetic and Pharmacodynamic Endpoints in Contemporary Drug Discovery and Development

2003 • 150 citations

The Akt/PKB Family of Protein Kinases: A Review of Small Molecule Inhibitors and Progress Towards Target Validation

2005 • 148 citations

Targeting protein–protein interactions for cancer therapy

2005 • 147 citations

Design and Discovery of Small Molecules Targeting Raf-1 Kinase

2002 • 146 citations

Applications of high-throughput ADME in drug discovery

2004 • 142 citations

A Three-Hybrid Approach to Scanning the Proteome for Targets of Small Molecule Kinase Inhibitors

2004 • 137 citations

Synthesis and Target Identification of Hymenialdisine Analogs

2004 • 130 citations

Finding the target after screening the phenotype

2005 • 128 citations

Mutation of Threonine 766 in the Epidermal Growth Factor Receptor Reveals a Hotspot for Resistance Formation against Selective Tyrosine Kinase Inhibitors

2003 • 116 citations

Hexachlorophene Inhibits Wnt/β-Catenin Pathway by Promoting Siah-Mediated β-Catenin Degradation

2006 • 114 citations

A Genome-Wide Overexpression Screen in Yeast for Small-Molecule Target Identification

2005 • 112 citations

Identification of Compounds with Nanomolar Binding Affinity for Checkpoint Kinase-1 Using Knowledge-Based Virtual Screening

2004 • 110 citations

Components of Successful Lead Generation

2005 • 108 citations

Auditing the pharmacological accounts for Hsp90 molecular chaperone inhibitors: unfolding the relationship between pharmacokinetics and pharmacodynamics.

2003 • 108 citations

Complex phenotypic assays in high-throughput screening

2004 • 99 citations

Chemical Genetic Modifier Screens

2003 • 87 citations

The Discovery of NVP-LAQ824: From Concept to Clinic

2003 • 86 citations

Novel chemical genetic approaches to the discovery of signal transduction inhibitors

2002 • 81 citations

Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases

2006 • 75 citations

Inhibitors of the HSP90 Molecular Chaperone: Attacking the Master Regulator in Cancer

2006 • 72 citations

Site-directed irreversible inhibitors of the erbB family of receptor tyrosine kinases as novel chemotherapeutic agents for cancer.

2000 • 70 citations

Identification of Potent Ras Signaling Inhibitors by Pathway‐Selective Phenotype‐Based Screening

2004 • 68 citations

Gastrointestinal stromal tumours (GIST): biology and treatment

2002 • 68 citations

Challenges of PK/PD measurements in modern drug development

2002 • 67 citations

Drugging the PI3 kinome

2006 • 63 citations

The Purinome, a Complex Mix of Drug and Toxicity Targets

2006 • 55 citations

Biopharmaceutics Classification by High Throughput Solubility Assay and PAMPA

2004 • 53 citations

RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors

2005 • 51 citations

Identification of Akt Pathway Inhibitors Using Redistribution Screening on the FLIPR and the IN Cell 3000 Analyzer

2005 • 50 citations

Predicting drug-drug interactions in drug discovery: where are we now and where are we going?

2005 • 48 citations

Genomics and the second golden era of cancer drug development

2005 • 47 citations

Telomerase as a Target for Cancer Immunotherapy

2003 • 47 citations

Design and Synthesis of Potent Non-Polyglutamatable Quinazoline Antifolate Thymidylate Synthase Inhibitors

1999 • 45 citations

Cassette dosing pharmacokinetics of a library of 2,6,9-trisubstituted purine cyclin-dependent kinase 2 inhibitors prepared by parallel synthesis

2004 • 44 citations

High Throughput Screening for Protein Kinase Inhibitors

2005 • 42 citations

Preclinical pharmacokinetics and metabolism of a novel diaryl pyrazole resorcinol series of heat shock protein 90 inhibitors

2006 • 38 citations

Target‐Family‐Oriented Focused Libraries for Kinases—Conceptual Design Aspects and Commercial Availability

2005 • 38 citations

Drugging the Cancer Kinome: Progress and Challenges in Developing Personalized Molecular Cancer Therapeutics

2005 • 34 citations

Selective Kinase Inhibition by Exploiting Differential Pathway Sensitivity

2006 • 27 citations

Automated High Content Screening for Phosphoinositide 3 Kinase Inhibition Using an AKT1 Redistribution Assay

2006 • 27 citations

Exploring the sounds of silence: RNAi-mediated gene silencing for target identification and validation

2005 • 23 citations

Design and Synthesis of Protein Superfamily-Targeted Chemical Libraries for Lead Identification and Optimization

2005 • 22 citations

Compound Selection and Filtering in Library Design

2005 • 19 citations

Identification of Inhibitors of the Kinase Activity of Oncogenic V600EBRAF in an Enzyme Cascade High-Throughput Screen

2006 • 19 citations

Stuart Schreiber: biology from a chemist’s perspective

2004 • 17 citations

322 Novel isoquinoline-5-sulfonamides as biochemical and cellular inhibitors of PKB/AKt

2004 • 3 citations