How were new medicines discovered?

Cell Signaling by Receptor Tyrosine Kinases

2010 • 7,477 citations

Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade

1997 • 7,177 citations

Goodman & Gilman's The Pharmacological Basis of Therapeutics

1985 • 7,054 citations

Goodman and Gilman's the Pharmacological Basis of Therapeutics

1986 • 6,964 citations

Natural Products as Sources of New Drugs over the Last 25 Years

2007 • 5,425 citations

How many drug targets are there?

2006 • 3,319 citations

Molecular basis of agonism and antagonism in the oestrogen receptor

1997 • 3,285 citations

Epigenetics in human disease and prospects for epigenetic therapy

2004 • 3,142 citations

How to improve R&D productivity: the pharmaceutical industry's grand challenge

2010 • 3,112 citations

Enzyme structure and mechanism

1977 • 2,935 citations

Enzyme structure and mechanism

1978 • 2,897 citations

Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer

2004 • 2,481 citations

The biology of incretin hormones

2006 • 2,029 citations

In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship.

2003 • 1,939 citations

Protein therapeutics: a summary and pharmacological classification

2007 • 1,914 citations

The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP

2008 • 1,886 citations

Rational design of potent sialidase-based inhibitors of influenza virus replication

1993 • 1,819 citations

Discovery and development of sorafenib: a multikinase inhibitor for treating cancer

2006 • 1,693 citations

Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.

1975 • 1,605 citations

Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety

2001 • 1,538 citations

Photodynamic therapy with endogenous protoporphyrin

1990 • 1,519 citations

Renal-Cell Carcinoma

2005 • 1,508 citations

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

2002 • 1,349 citations

Drug–target residence time and its implications for lead optimization

2006 • 1,332 citations

Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors

2003 • 1,236 citations

Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors

2003 • 1,172 citations

Lessons from 60 years of pharmaceutical innovation

2009 • 1,168 citations

Impact of high-throughput screening in biomedical research

2011 • 1,168 citations

Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug

2007 • 1,142 citations

Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in Cells

2000 • 1,122 citations

A potent specific pure antiestrogen with clinical potential.

1991 • 1,111 citations

Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity

2005 • 1,109 citations

Functional Selectivity and Classical Concepts of Quantitative Pharmacology

2006 • 1,076 citations

Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders

2008 • 990 citations

Pharmacologic Analysis of Drug Receptor Interaction

1988 • 936 citations

Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation

2005 • 922 citations

Aripiprazole, a Novel Antipsychotic, Is a High-Affinity Partial Agonist at Human Dopamine D2 Receptors

2002 • 896 citations

The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.

1975 • 856 citations

Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond

2006 • 847 citations

Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist—a review of preclinical data

1999 • 841 citations

Molecular Mechanisms of Local Anesthesia

1990 • 840 citations

Proteasome inhibitors in cancer therapy

2017 • 830 citations

Catching Up on Schizophrenia

2000 • 815 citations

Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells.

1993 • 814 citations

Drugs, their targets and the nature and number of drug targets

2006 • 796 citations

Arzneimittelforschung

2015 • 736 citations

Integrase inhibitors to treat HIV/Aids

2005 • 680 citations

Electrophysiological Effects of Ranolazine, a Novel Antianginal Agent With Antiarrhythmic Properties

2004 • 679 citations

Effects of Ranolazine With Atenolol, Amlodipine, or Diltiazem on Exercise Tolerance and Angina Frequency in Patients With Severe Chronic Angina<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

2004 • 657 citations

Structure-activity relationship in heparin: A synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity

1983 • 651 citations

The odyssey of marine pharmaceuticals: a current pipeline perspective

2010 • 633 citations

Strategies in the design of antiviral drugs

2002 • 631 citations

Discovery of Raltegravir, a Potent, Selective Orally Bioavailable HIV-Integrase Inhibitor for the Treatment of HIV-AIDS Infection

2008 • 612 citations

The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20

2006 • 592 citations

Seven Transmembrane Receptors as Shapeshifting Proteins: The Impact of Allosteric Modulation and Functional Selectivity on New Drug Discovery

2010 • 554 citations

Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina

2004 • 544 citations

Studies leading to the identification of ZD1839 (iressa™): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer

2001 • 534 citations

Structure-based design of aliskiren, a novel orally effective renin inhibitor

2003 • 499 citations

Residence Time of Receptor−Ligand Complexes and Its Effect on Biological Function

2008 • 497 citations

N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis.

1994 • 453 citations

Inhibition of the immune response by rapamycin, a new antifungal antibiotic

1977 • 444 citations

Probing the links between in vitro potency, ADMET and physicochemical parameters

2011 • 442 citations

The Human Estrogen Receptor-α Is a Ubiquitinated Protein Whose Stability Is Affected Differentially by Agonists, Antagonists, and Selective Estrogen Receptor Modulators

2001 • 422 citations

Second generation hybrid polar compounds are potent inducers of transformed cell differentiation.

1996 • 421 citations

Drug–target residence time: critical information for lead optimization

2010 • 412 citations

FRAP reveals that mobility of oestrogen receptor-α is ligand- and proteasome-dependent

2000 • 390 citations

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

2004 • 370 citations

Strategies for Discovering and Derisking Covalent, Irreversible Enzyme Inhibitors

2010 • 366 citations

Non-peptide arginine-vasopressin antagonists: the vaptans

2008 • 356 citations

Conserved Binding Mode of Human β₂ Adrenergic Receptor Inverse Agonists and Antagonist Revealed by X-ray Crystallography

2010 • 352 citations

Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels

1989 • 347 citations

Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin

1988 • 338 citations

Diverse mechanisms of antiepileptic drugs in the development pipeline

2006 • 336 citations

Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity.

1987 • 328 citations

HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase

2000 • 314 citations

HIV drug development: the next 25 years

2007 • 311 citations

Development of daptomycin for Gram-positive infections

2000 • 308 citations

Target discovery

2003 • 298 citations

Tetrahydrobiopterin as an Alternative Treatment for Mild Phenylketonuria

2002 • 298 citations

The CCR5 Receptor-Based Mechanism of Action of 873140, a Potent Allosteric Noncompetitive HIV Entry Inhibitor

2005 • 297 citations

New thrombopoietic growth factors

2007 • 294 citations

Therapeutic Strategies Based on Glucagon-Like Peptide 1

2004 • 293 citations

New Thrombopoietic Growth Factors

2009 • 291 citations

The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning

2008 • 283 citations

Tiotropium (SPIRIVA™): Mechanistical considerations and clinical profile in obstructive lung disease

1999 • 275 citations

7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity.

1995 • 268 citations

Pharmacologic analysis of drug-receptor interaction

1995 • 255 citations

Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency

2005 • 254 citations

Pathologically activated therapeutics for neuroprotection

2007 • 252 citations

A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia.

1993 • 250 citations

SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents

2004 • 231 citations

ucb L059, a novel anti-convulsant drug: pharmacological profile in animais

1992 • 208 citations

Mechanism of action of the oxazolidinone antibacterial agents

1999 • 206 citations

Role of Induced Fit in Enzyme Specificity: A Molecular Forward/Reverse Switch

2008 • 189 citations

The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency

2004 • 187 citations

The control of fertility

1965 • 185 citations

A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved?

1984 • 183 citations

The beautiful cell: high-content screening in drug discovery

2010 • 173 citations

Mifepristone (RU486): A review

1997 • 163 citations

Preliminary studies on a more effective phototoxic agent than hematoporphyrin.

1987 • 162 citations

Oxazolidinone Antibacterial Agents

1996 • 159 citations

New therapeutics that antagonize endothelin: promises and frustrations

2002 • 146 citations

Novel Antipsychotic Agents with Dopamine Autoreceptor Agonist Properties: Synthesis and Pharmacology of 7-[4-(4-Phenyl-1-piperazinyl)butoxy]-3,4-dihydro-2(1H)-quinolinone Derivatives

1998 • 140 citations

The Adamantyl Group in Medicinal Agents. I. Hypoglycemic N-Arylsulfonyl-N'-adamantylureas

1963 • 138 citations

Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections

2006 • 136 citations

Nitazoxanide in the Treatment of Taenia Saginata and Hymenolepis nana Infections

1984 • 133 citations

Synthesis of a Novel Series of Tricyclic Indan Derivatives as Melatonin Receptor Agonists

2002 • 131 citations

Azacitidine

2005 • 130 citations

Regio and stereospecific synthesis of 11β-substituted 19-norsteroids

1981 • 130 citations

Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide.

2000 • 126 citations

Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors.

2001 • 123 citations

Vigilance and Validation: Keys to Success in RNAi Screening

2010 • 122 citations

Echinocandin inhibition of 1,3-β-D-glucan synthase from Candida albicans

1984 • 120 citations

Structure of the Ferrous Form of (4-Hydroxyphenyl)pyruvate Dioxygenase from Streptomyces avermitilis in Complex with the Therapeutic Herbicide, NTBC^,

2004 • 119 citations

Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor

2002 • 117 citations

Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461

1995 • 112 citations

Dopamine receptor agonists, partial agonists and psychostimulant addiction

1994 • 110 citations

Allosteric Receptors: From Electric Organ to Cognition

2010 • 105 citations

From toxicological problem to therapeutic use: The discovery of the mode of action of 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC), its toxicology and development as a drug

1998 • 102 citations

Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.

1991 • 98 citations

Designing transient binding drugs: A new concept for drug discovery

2008 • 95 citations

In vitro antifungal activities and in vivo efficacies of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991, tetrahydroechinocandin B, and L-687,781, a papulacandin

1992 • 94 citations

Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif

2005 • 92 citations

Structural Modification of the P2‘ Position of 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamides: The Discovery of Aliskiren, a Potent Nonpeptide Human Renin Inhibitor Active after Once Daily Dosing in Marmosets

2007 • 91 citations

Effects of the novel antipsychotic agent 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro -2(1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary gland.

1996 • 90 citations

Competitiveness in follow-on drug R&D: a race or imitation?

2010 • 89 citations

Biochemical Mechanisms of New Molecular Entities (NMEs) Approved by United States FDA During 2001-2004: Mechanisms Leading to Optimal Efficacy and Safety

2006 • 89 citations

2-Amino-6-methoxypurine arabinoside: an agent for T-cell malignancies.

1995 • 88 citations

N-(Cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2

1989 • 79 citations

Mechanisms for T-cell selective cytotoxicity of arabinosylguanine

2003 • 78 citations

Immunopharmacological Studies on TBX, a New Antiallergic Drug (1) Inhibitory Effects on Passive Cutaneous Anaphylaxis in Rats and Guinea Pigs

1988 • 77 citations

3-Sulfamoylmethyl-1,2-benzisoxazole, a new type of anticonvulsant drug. Pharmacological profile.

1980 • 74 citations

N-Acylphenylalanines and related compounds. A new class of oral hypoglycemic agents

1988 • 73 citations

Experimental Porphyric Neuropathy: A Preliminary Report

1981 • 73 citations

Extreme Sensitivity of Enveloped Viruses, Including Herpes Simplex, to Long-Chain Unsaturated Monoglycerides and Alcohols

1979 • 71 citations

Verteporfin: a milestone in opthalmology and photodynamic therapy

2001 • 70 citations

Pleuromutilin antibiotics

2000 • 69 citations

Interaction of (4-Hydroxyphenyl)pyruvate Dioxygenase with the Specific Inhibitor 2-[2-Nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione

2003 • 69 citations

The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation

2009 • 68 citations

Using Lidocaine and Benzocaine to Link Sodium Channel Molecular Conformations to State-Dependent Antiarrhythmic Drug Affinity

2009 • 67 citations

Chemokine Antagonists as Therapeutics: Focus on HIV-1

2006 • 64 citations

An enzymic synthesis of purine d-Arabinonucleosides

1981 • 62 citations

Green tea catechins for treatment of external genital warts

2008 • 61 citations

Applications of Binding Kinetics to Drug Discovery

2008 • 57 citations

Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1

2003 • 56 citations

Inactivation of Lipid-Containing Viruses by Long-Chain Alcohols

1977 • 54 citations

Neurokinin 1 receptor antagonists--current prospects.

2007 • 54 citations

THE INACTIVATION OF THE VIRUS OF EPIDEMIC INFLUENZA BY SOAPS

1940 • 53 citations

Purine nucleoside antimetabolites in development for the treatment of cancer.

2004 • 50 citations

Nelarabine

2006 • 46 citations

Long-lasting angiotensin type 1 receptor binding and protection by candesartan: comparison with other biphenyl-tetrazole sartans

2006 • 42 citations

Innovations and Challenges in Renal Cancer

2004 • 40 citations

Misconceptions About Calcimimetics

2006 • 38 citations

7-[3-(4-[2,3-dimethylphenyl]piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392), a presynaptic dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist

1988 • 35 citations

Transcript Profiling and RNA Interference as Tools To Identify Small Molecule Mechanisms and Therapeutic Potential

2010 • 31 citations

Systems and integrative biology as alternative guises for pharmacology: Prime time for an iPharm concept?

2005 • 30 citations

Diseases of Amino Acid Metabolism

1999 • 30 citations

Ramelteon

2005 • 30 citations

Comparative Pharmacodynamics and Pharmacokinetics of Candesartan and Losartan in Man

2000 • 28 citations

An assessment of rufinamide as an anti-epileptic in comparison with other drugs in clinical development

2000 • 28 citations

Raloxifene: Magic bullet for heart and bone?

1998 • 26 citations

Studies on 2-oxoquinoline derivatives as blood platelet aggregation inhibitors. I. Alkyl 4-(2-oxo-1,2,3,4-tetrahydro-6-quinolyloxy)butyrates and related compounds.

1983 • 25 citations

Phenotypic Screening Strategies for Neurodegenerative Diseases: A Pathway to Discover Novel Drug Candidates and Potential Disease Targets or Mechanisms

2010 • 23 citations

Rethinking Target Discovery in Polygenic Diseases

2006 • 19 citations

Ranolazine, a Novel Agent for Chronic Stable Angina

2006 • 16 citations

Development of a Synthetic Heparin Pentasaccharide: Fondaparinux.

2002 • 13 citations

Introduction to the Proteasome and its Inhibitors

2004 • 7 citations

Long-lasting AT1 receptor binding and protection by Candesartan: comparison to other biphenyl-tetrazole sartans

2006 • 6 citations

Deleted Work

1955 • 0 citations