The promise and peril of chemical probes

Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action

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A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).

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Specificity and mechanism of action of some commonly used protein kinase inhibitors.

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Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide-dependent protein kinase and protein kinase C

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Staurosporine, a potent inhibitor of phospholipidCa++dependent protein kinase

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Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

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Click Chemistry for Drug Development and Diverse Chemical–Biology Applications

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Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells

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Specificity and mechanism of action of some commonly used protein kinase inhibitors

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Targeting bromodomains: epigenetic readers of lysine acetylation

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Chemistry: Chemical con artists foil drug discovery

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Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism

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SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1

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Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells

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Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors

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Liver X receptors in lipid metabolism: opportunities for drug discovery

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Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

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Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9

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Identification of a Nonsteroidal Liver X Receptor Agonist through Parallel Array Synthesis of Tertiary Amines

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Target validation using chemical probes

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Too many roads not taken

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The art of the chemical probe

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Probing the Probes: Fitness Factors For Small Molecule Tools

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Recognizing and exploiting differences between RNAi and small-molecule inhibitors

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Drugging the PI3 Kinome: From Chemical Tools to Drugs in the Clinic

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Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages

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The specificities of small molecule inhibitors of the TGFß and BMP pathways

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Determining target engagement in living systems

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The human genome and drug discovery after a decade. Roads (still) not takenPreprint

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Mechanistic and Pharmacological Characterization of PF-04457845: A Highly Potent and Selective Fatty Acid Amide Hydrolase Inhibitor That Reduces Inflammatory and Noninflammatory Pain

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Different forms of cell death induced by putative BCL2 inhibitors

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Iniparib Nonselectively Modifies Cysteine-Containing Proteins in Tumor Cells and Is Not a Bona Fide PARP Inhibitor

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3-Deazaneplanocin: A new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60

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BET bromodomain inhibitors: a patent review

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Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases

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Colloidal Aggregation Causes Inhibition of G Protein-Coupled Receptors

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On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin

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Synthesis, Biological Evaluation, and Molecular Modeling Investigation of New Chiral Fibrates with PPARα and PPARγ Agonist Activity

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Recently targeted kinases and their inhibitors—the path to clinical trials

Knapp, S., & Sundström, M. (2014) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2014.07.015 · Cited by 49 · see citing works

Target (In)Validation: A Critical, Sometimes Unheralded, Role of Modern Medicinal Chemistry

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The frequency of Mislabelled chemicals from commercial suppliers

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DREADDs for neuroscientists

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Counting on natural products for drug design

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Towards the sustainable discovery and development of new antibiotics

Miethke, M., Pieroni, M., Weber, T., Brönstrup, M., Hammann, P., Halby, L., Arimondo, P. B., Glaser, P., Aigle, B., Bode, H. B., et al. (2021) · Nature Reviews Chemistry · doi:10.1038/s41570-021-00313-1 · Cited by 1,184 · see citing works

Opportunities and challenges in phenotypic drug discovery: an industry perspective

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Modern advances in heterocyclic chemistry in drug discovery

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QSAR without borders

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Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017─Utility and Limitations

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Feeling Nature’s PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)

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Emerging therapeutic opportunities for integrin inhibitors

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Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease

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Open Targets Platform: supporting systematic drug–target identification and prioritisation

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Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds

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Open Targets Platform: new developments and updates two years on

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Bromodomains: a new target class for drug development

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Protein arginine methylation: from enigmatic functions to therapeutic targeting

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The Necessary Nitrogen Atom: A Versatile High-Impact Design Element for Multiparameter Optimization

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Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

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A Perspective on the Kinetics of Covalent and Irreversible Inhibition

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Atropisomerism in Medicinal Chemistry: Challenges and Opportunities

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Click Chemistry in Proteomic Investigations

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Broad-Spectrum Kinase Profiling in Live Cells with Lysine-Targeted Sulfonyl Fluoride Probes

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Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors

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DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information

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Phenotypic drug discovery: recent successes, lessons learned and new directions

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The emerging role of mass spectrometry-based proteomics in drug discovery

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Illuminating the dark phosphoproteome

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Inhibitors of Protein Methyltransferases and Demethylases

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Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement

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Modulators of 14-3-3 Protein–Protein Interactions

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Docking Screens for Novel Ligands Conferring New Biology

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The PROTACtable genome

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Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent

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Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

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Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

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Improving target assessment in biomedical research: the GOT-IT recommendations

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Chemical probes and drug leads from advances in synthetic planning and methodology

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Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor

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Loss-of-function genetic tools for animal models: cross-species and cross-platform differences

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Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology

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A critical overview of computational approaches employed for COVID-19 drug discovery

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Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain

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Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

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Disrupting Acetyl-Lysine Recognition: Progress in the Development of Bromodomain Inhibitors

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Applications of chemogenomic library screening in drug discovery

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Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

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Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation

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BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector ProteinsPreprint

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Opportunities and challenges in translational science

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Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase: Structure–Activity Relationships Leading to the Chemical Probe (2 S ,4 R )-1-(( S )-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy- N -(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298)

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The Ecstasy and Agony of Assay Interference Compounds

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The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

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New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome

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Target 2035: probing the human proteome

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CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

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Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy

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Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations

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Design and characterization of bivalent BET inhibitors

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The role of reversible and irreversible covalent chemistry in targeted protein degradation

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Drug Target Commons: A Community Effort to Build a Consensus Knowledge Base for Drug-Target Interactions

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RNA-modifying proteins as anticancer drug targets

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Progress towards a public chemogenomic set for protein kinases and a call for contributions

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The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases

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Activity-Based Sensing for Site-Specific Proteomic Analysis of Cysteine Oxidation

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Targeting the Small GTPase Superfamily through Their Regulatory Proteins

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Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells

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Exploring and Understanding the Biochemical Diversity of the Human Microbiota

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A chemical biology toolbox to study protein methyltransferases and epigenetic signaling

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Chemoproteomics and Chemical Probes for Target Discovery

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Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

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An αv‐RGD Integrin Inhibitor Toolbox: Drug Discovery Insight, Challenges and Opportunities

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Small Molecule Inhibitors of Protein Arginine Methyltransferases

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Genotoxicity testing: progress and prospects for the next decade

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Structure-based drug design: aiming for a perfect fit

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Non-kinase targets of protein kinase inhibitors

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A fast and specific fluorescent probe for thioredoxin reductase that works via disulphide bond cleavage

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Protein S-Glyco-Modification through an Elimination–Addition Mechanism

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canSAR: update to the cancer translational research and drug discovery knowledgebase

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Transcription Factor Inhibition: Lessons Learned and Emerging Targets

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Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

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Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target

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Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit

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Proteostasis in Huntington's disease: disease mechanisms and therapeutic opportunities

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Irreproducibility in Preclinical Biomedical Research: Perceptions, Uncertainties, and Knowledge Gaps

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Chemical Biology Probes from Advanced DNA-encoded Libraries

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Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors

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A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization

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Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes

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Donated chemical probes for open science

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The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification

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The emerging role of lysine methyltransferase SETD8 in human diseases

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Extracellular vesicle drug occupancy enables real-time monitoring of targeted cancer therapy

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Badapple: promiscuity patterns from noisy evidence

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Nonparametric Analysis of Thermal Proteome Profiles Reveals Novel Drug-binding Proteins*

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Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe

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Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor

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Dual action antifungal small molecule modulates multidrug efflux and TOR signaling

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A Cell Biologist’s Field Guide to Aurora Kinase Inhibitors

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Medicinal chemistry in drug discovery in big pharma: past, present and future

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The Chemical Probes Portal: an expert review-based public resource to empower chemical probe assessment, selection and use

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Probing questions

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