Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery.

PubWeight™: 0.75‹?›

🔗 View Article (PMID 27449257)

Published in Curr Top Med Chem on July 19, 2016

Authors

Kenneth K Hallenbeck, David M Turner, Adam R Renslo, Michelle R Arkin1

Author Affiliations

1: Department of Pharmaceutical Chemistry, University of California, San Francisco, Box 2552, San Francisco, CA 94158, USA. michelle.arkin@ucsf.edu.

Articles cited by this

Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med (2005) 25.93

Non-Darwinian evolution. Science (1969) 14.05

Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature (2007) 9.12

The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A (2008) 8.08

AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med (2015) 7.11

Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature (2009) 7.05

Ligand efficiency: a useful metric for lead selection. Drug Discov Today (2004) 6.60

New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem (2010) 6.54

Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med (2015) 6.28

A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem (2002) 5.67

A decade of fragment-based drug design: strategic advances and lessons learned. Nat Rev Drug Discov (2007) 4.82

Drug-target residence time and its implications for lead optimization. Nat Rev Drug Discov (2006) 4.56

Convergent solutions to binding at a protein-protein interface. Science (2000) 4.47

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature (2013) 4.43

Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst (2001) 4.25

The resurgence of covalent drugs. Nat Rev Drug Discov (2011) 4.09

Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature (2010) 4.04

A 'rule of three' for fragment-based lead discovery? Drug Discov Today (2003) 3.45

Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. J Clin Oncol (2010) 3.40

Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem (2007) 2.96

Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov (2013) 2.93

Site-directed ligand discovery. Proc Natl Acad Sci U S A (2000) 2.58

Discovery of an allosteric site in the caspases. Proc Natl Acad Sci U S A (2004) 2.51

The rise of fragment-based drug discovery. Nat Chem (2009) 2.46

Is there a difference between leads and drugs? A historical perspective. J Chem Inf Comput Sci (2001) 2.38

LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol (2013) 2.37

Chemistry: Chemical con artists foil drug discovery. Nature (2014) 2.36

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State. Cancer Discov (2016) 2.35

Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. ACS Chem Biol (2009) 2.23

A common allosteric site and mechanism in caspases. Proc Natl Acad Sci U S A (2006) 2.12

Binding of small molecules to an adaptive protein-protein interface. Proc Natl Acad Sci U S A (2003) 1.78

Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol (2015) 1.77

Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides. Proc Natl Acad Sci U S A (2006) 1.73

Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles. Nat Chem Biol (2012) 1.67

Covalent docking of large libraries for the discovery of chemical probes. Nat Chem Biol (2014) 1.66

Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis (2013) 1.64

Two-state selection of conformation-specific antibodies. Proc Natl Acad Sci U S A (2009) 1.40

An allosteric circuit in caspase-1. J Mol Biol (2008) 1.38

Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor. Angew Chem Int Ed Engl (2013) 1.34

Turning a protein kinase on or off from a single allosteric site via disulfide trapping. Proc Natl Acad Sci U S A (2011) 1.33

Route to three-dimensional fragments using diversity-oriented synthesis. Proc Natl Acad Sci U S A (2011) 1.33

Lining the pockets of kinases and phosphatases. Curr Opin Struct Biol (2006) 1.30

Chemistry and biology of resorcylic acid lactones. Chem Commun (Camb) (2006) 1.29

Cysteine residues exposed on protein surfaces are the dominant intramitochondrial thiol and may protect against oxidative damage. FEBS J (2010) 1.28

Strategies for discovering and derisking covalent, irreversible enzyme inhibitors. Future Med Chem (2010) 1.27

The FTMap family of web servers for determining and characterizing ligand-binding hot spots of proteins. Nat Protoc (2015) 1.26

In situ assembly of enzyme inhibitors using extended tethering. Nat Biotechnol (2003) 1.11

Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine. Nat Chem Biol (2010) 1.11

PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS. J Med Chem (2015) 1.10

The 'rule of three' for fragment-based drug discovery: where are we now? Nat Rev Drug Discov (2013) 1.07

Electrophilic fragment-based design of reversible covalent kinase inhibitors. J Am Chem Soc (2013) 1.06

Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators. J Med Chem (2013) 1.04

In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Proc Natl Acad Sci U S A (2014) 1.02

Chemical and computational methods for the characterization of covalent reactive groups for the prospective design of irreversible inhibitors. J Med Chem (2014) 1.01

A fragment-based method to discover irreversible covalent inhibitors of cysteine proteases. J Med Chem (2014) 1.00

Dissecting an allosteric switch in caspase-7 using chemical and mutational probes. J Biol Chem (2009) 1.00

Fragment-based lead discovery and design. J Chem Inf Model (2014) 0.99

Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei [corrected]. Elife (2013) 0.98

Measurement and estimation of electrophilic reactivity for predictive toxicology. Chem Rev (2011) 0.96

A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity. Crit Rev Toxicol (2011) 0.96

Fragment based drug design: from experimental to computational approaches. Curr Med Chem (2012) 0.95

Thermodynamic analysis of water molecules at the surface of proteins and applications to binding site prediction and characterization. Proteins (2011) 0.95

Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target. Beilstein J Org Chem (2013) 0.95

Drug discovery considerations in the development of covalent inhibitors. Bioorg Med Chem Lett (2013) 0.94

Antitumor efficacy of hypothemycin, a new Ras-signaling inhibitor. Jpn J Cancer Res (1999) 0.94

Integrating fragment assembly and biophysical methods in the chemical advancement of small-molecule antagonists of IL-2: an approach for inhibiting protein-protein interactions. J Med Chem (2004) 0.92

Discovery of multiple hidden allosteric sites by combining Markov state models and experiments. Proc Natl Acad Sci U S A (2015) 0.92

Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery. Bioorg Med Chem Lett (2011) 0.91

FP Tethering: a screening technique to rapidly identify compounds that disrupt protein-protein interactions. Medchemcomm (2014) 0.91

Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach. J Med Chem (2015) 0.87

Tricyclic covalent inhibitors selectively target Jak3 through an active site thiol. J Biol Chem (2014) 0.86

Targeting a cryptic allosteric site for selective inhibition of the oncogenic protein tyrosine phosphatase Shp2. Biochemistry (2015) 0.84

Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies. Drug Discov Today (2015) 0.83

In vivo efficacy of natural product-inspired irreversible kinase inhibitors. Chembiochem (2010) 0.82

A proposed screening paradigm for discovery of covalent inhibitor drugs. Drug Metab Lett (2014) 0.79

Prediction of substrates for glutathione transferases by covalent docking. J Chem Inf Model (2014) 0.79

Pharmacokinetic characterization of a natural product-inspired novel MEK1 inhibitor E6201 in preclinical species. Cancer Chemother Pharmacol (2011) 0.78

Covalent binding to glutathione of the DNA-alkylating antitumor agent, S23906-1. Eur J Biochem (2003) 0.78

Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release. J Med Chem (2015) 0.78

Covalent targeting of acquired cysteines in cancer. Curr Opin Chem Biol (2015) 0.78

Strategies for profiling native S-nitrosylation. Biopolymers (2014) 0.78

Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies. Ann N Y Acad Sci (2015) 0.77

Efficient and facile synthesis of acrylamide libraries for protein-guided tethering. Org Lett (2015) 0.77

Rational design of allosteric-inhibition sites in classical protein tyrosine phosphatases. Bioorg Med Chem (2015) 0.77

Discovery of Bivalent Kinase Inhibitors via Enzyme-Templated Fragment Elaboration. ACS Med Chem Lett (2015) 0.76

Articles by these authors

Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife (2013) 1.85

Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening. PLoS Negl Trop Dis (2009) 1.74

Discovery of 2-aminothiazoles as potent antiprion compounds. J Virol (2009) 1.51

Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett (2009) 1.33

2-Aminothiazoles as therapeutic leads for prion diseases. J Med Chem (2011) 1.19

Drug resistance confounding prion therapeutics. Proc Natl Acad Sci U S A (2013) 1.10

Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg Med Chem (2007) 1.09

Predicting binding to p-glycoprotein by flexible receptor docking. PLoS Comput Biol (2011) 1.07

Identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system. PLoS Negl Trop Dis (2011) 1.07

Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes. Bioorg Med Chem Lett (2007) 1.00

Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei [corrected]. Elife (2013) 0.98

Divergent modes of enzyme inhibition in a homologous structure-activity series. J Med Chem (2009) 0.96

A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels. ACS Chem Biol (2013) 0.95

Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target. Beilstein J Org Chem (2013) 0.95

Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl Trop Dis (2011) 0.93

A fragmenting hybrid approach for targeted delivery of multiple therapeutic agents to the malaria parasite. ChemMedChem (2011) 0.93

Pharmacokinetics and metabolism of 2-aminothiazoles with antiprion activity in mice. Pharm Res (2013) 0.92

Investigating the antimalarial action of 1,2,4-trioxolanes with fluorescent chemical probes. J Med Chem (2011) 0.92

Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease. Br J Haematol (2014) 0.91

Simple one-pot synthesis of disulfide fragments for use in disulfide-exchange screening. ACS Comb Sci (2011) 0.90

Predicting and improving the membrane permeability of peptidic small molecules. J Med Chem (2012) 0.90

Efficient and stereocontrolled synthesis of 1,2,4-trioxolanes useful for ferrous iron-dependent drug delivery. Org Lett (2014) 0.87

Biaryl amides and hydrazones as therapeutics for prion disease in transgenic mice. J Pharmacol Exp Ther (2013) 0.86

Ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo. Proc Natl Acad Sci U S A (2013) 0.86

Drug delivery to the malaria parasite using an arterolane-like scaffold. ChemMedChem (2014) 0.85

Ferrous iron-dependent delivery of therapeutic agents to the malaria parasite. Future Med Chem (2012) 0.83

Development of an ex vivo lymph node explant model for identification of novel molecules active against Leishmania major. Antimicrob Agents Chemother (2013) 0.82

Intramolecular [4 + 2] cycloadditions of iminoacetonitriles: a new class of azadienophiles for hetero Diels-Alder reactions. J Am Chem Soc (2003) 0.82

2-Aminothiazoles with improved pharmacotherapeutic properties for treatment of prion disease. ChemMedChem (2013) 0.81

Mechanistic and structural understanding of uncompetitive inhibitors of caspase-6. PLoS One (2012) 0.81

Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A β-lactamase. J Med Chem (2012) 0.80

Broad-spectrum allosteric inhibition of herpesvirus proteases. Biochemistry (2014) 0.80

Drug discovery for neglected tropical diseases at the Sandler Center. Future Med Chem (2011) 0.79

Successes and challenges in phenotype-based lead discovery for prion diseases. J Med Chem (2014) 0.79

Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles. Org Biomol Chem (2013) 0.79

Fluorous parallel synthesis of a piperazinedione-fused tricyclic compound library. J Comb Chem (2009) 0.79

Convergent evolution of chromatin modification by structurally distinct enzymes: comparative enzymology of histone H3 Lys²⁷ methylation by human polycomb repressive complex 2 and vSET. Biochem J (2013) 0.78

Antiprion compounds that reduce PrP(Sc) levels in dividing and stationary-phase cells. Bioorg Med Chem (2013) 0.78

Trifluoroacetic acid in 2,2,2-trifluoroethanol facilitates S(N)Ar reactions of heterocycles with arylamines. Chemistry (2014) 0.77

Tailoring small molecules for an allosteric site on procaspase-6. ChemMedChem (2013) 0.77

Fragment-based inhibitor discovery against β-lactamase. Future Med Chem (2014) 0.76

Electrostatic Potential Change in a Paired Epitope: A Novel Explanation for Bw4 Antibodies in Patients With B13 (Bw4) Antigens. Transplantation (2016) 0.76

Modulating caspase activity: beyond the active site. Curr Opin Struct Biol (2013) 0.75

Simple plate-based, parallel synthesis of disulfide fragments using the CuAAC click reaction. ACS Comb Sci (2014) 0.75

A practical synthesis of differentially protected 2-(hydroxymethyl)piperazines. J Org Chem (2007) 0.75