Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides.

PubWeight™: 1.42‹?› | Rank: Top 5%

🔗 View Article (PMID 22136469)

Published in J Med Chem on January 11, 2012

Authors

Paul Bamborough1, Hawa Diallo, Jonathan D Goodacre, Laurie Gordon, Antonia Lewis, Jonathan T Seal, David M Wilson, Michael D Woodrow, Chun-Wa Chung

Author Affiliations

1: Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Paul.a.Bamborough@gsk.com

Articles citing this

Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov (2012) 6.70

Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov (2014) 3.54

BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer (2012) 2.80

Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem (2012) 1.55

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci U S A (2013) 1.35

Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains. J Am Chem Soc (2014) 1.23

Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands. J Med Chem (2013) 1.09

Protein lysine acetylation by p300/CBP. Chem Rev (2015) 1.02

The bromodomain: from epigenome reader to druggable target. Biochim Biophys Acta (2014) 1.02

[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains. J Med Chem (2013) 1.01

Discovery of novel small-molecule inhibitors of BRD4 using structure-based virtual screening. J Med Chem (2013) 0.99

HIV/AIDS eradication. Bioorg Med Chem Lett (2013) 0.98

Fragment-based screening by protein crystallography: successes and pitfalls. Int J Mol Sci (2012) 0.96

Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol (2013) 0.93

Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors. ACS Med Chem Lett (2013) 0.93

Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. J Med Chem (2013) 0.93

Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives. Curr Pharm Des (2013) 0.91

1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain. ACS Med Chem Lett (2014) 0.88

Fragment-based drug discovery using a multidomain, parallel MD-MM/PBSA screening protocol. J Chem Inf Model (2013) 0.87

Biased multicomponent reactions to develop novel bromodomain inhibitors. J Med Chem (2014) 0.87

Selective Inhibition of CBX6: A Methyllysine Reader Protein in the Polycomb Family. ACS Med Chem Lett (2015) 0.87

Privileged diazepine compounds and their emergence as bromodomain inhibitors. Chem Biol (2014) 0.86

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains. Medchemcomm (2013) 0.84

9H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain. J Med Chem (2015) 0.84

Bromodomains: are readers right for epigenetic therapy? ACS Med Chem Lett (2012) 0.81

BET inhibition as a new strategy for the treatment of gastric cancer. Oncotarget (2016) 0.81

Design of small molecule epigenetic modulators. Bioorg Med Chem Lett (2013) 0.81

Observed bromodomain flexibility reveals histone peptide- and small molecule ligand-compatible forms of ATAD2. Biochem J (2015) 0.80

HADDOCK(2P2I): a biophysical model for predicting the binding affinity of protein-protein interaction inhibitors. J Chem Inf Model (2014) 0.79

Translational synthetic chemistry. Nat Chem Biol (2013) 0.77

Rapid and Reliable Binding Affinity Prediction of Bromodomain Inhibitors: A Computational Study. J Chem Theory Comput (2017) 0.75

Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6. Mar Drugs (2017) 0.75

Articles by these authors

Suppression of inflammation by a synthetic histone mimic. Nature (2010) 8.80

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. Nature (2004) 5.24

Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res (2006) 4.20

A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature (2012) 4.08

A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors. Genome Res (2006) 2.71

Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains. J Med Chem (2013) 2.09

Removal of oxidative DNA damage via FEN1-dependent long-patch base excision repair in human cell mitochondria. Mol Cell Biol (2008) 1.95

DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst) (2013) 1.85

Differential expansion of zinc-finger transcription factor loci in homologous human and mouse gene clusters. Genome Res (2003) 1.77

XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Res (2004) 1.70

Is the use of arch bars or interdental wire fixation necessary for successful outcomes in the open reduction and internal fixation of mandibular angle fractures? J Oral Maxillofac Surg (2008) 1.64

Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage. Cancer Epidemiol Biomarkers Prev (2006) 1.59

Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic Acids Res (2005) 1.59

Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes. Genome Res (2006) 1.54

Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res (2003) 1.53

Hyperpolarized 13C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging. Proc Natl Acad Sci U S A (2011) 1.52

A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents. Mol Cancer Res (2007) 1.52

Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy. J Exp Med (2012) 1.42

Protein-protein interactions and posttranslational modifications in mammalian base excision repair. Free Radic Biol Med (2005) 1.42

Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev (2013) 1.41

Hyperpolarized [2-13C]-fructose: a hemiketal DNP substrate for in vivo metabolic imaging. J Am Chem Soc (2009) 1.38

Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice. PLoS Genet (2009) 1.37

Overview of base excision repair biochemistry. Curr Mol Pharmacol (2012) 1.36

Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat Immunol (2010) 1.35

Human apurinic/apyrimidinic endonuclease 1. Antioxid Redox Signal (2013) 1.34

The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase beta. Nucleic Acids Res (2006) 1.34

Identification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1. PLoS One (2009) 1.32

Processing of bistranded abasic DNA clusters in gamma-irradiated human hematopoietic cells. Nucleic Acids Res (2004) 1.31

GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther (2007) 1.30

Mitochondrial DNA, base excision repair and neurodegeneration. DNA Repair (Amst) (2008) 1.27

Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane. FASEB J (2010) 1.25

Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A). Bioorg Med Chem Lett (2012) 1.24

Imaging of blood flow using hyperpolarized [(13)C]urea in preclinical cancer models. J Magn Reson Imaging (2011) 1.23

Pathways for repairing and tolerating the spectrum of oxidative DNA lesions. Cancer Lett (2012) 1.20

Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III. J Mol Biol (2002) 1.19

BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS One (2013) 1.19

Aprataxin localizes to mitochondria and preserves mitochondrial function. Proc Natl Acad Sci U S A (2011) 1.19

Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. J Mol Biol (2008) 1.19

Hyperpolarized (13)C spectroscopy and an NMR-compatible bioreactor system for the investigation of real-time cellular metabolism. Magn Reson Med (2010) 1.18

Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res (2009) 1.18

Direct and indirect roles of RECQL4 in modulating base excision repair capacity. Hum Mol Genet (2009) 1.18

Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates. Nucleic Acids Res (2007) 1.18

The involvement of DNA-damage and -repair defects in neurological dysfunction. Am J Hum Genet (2008) 1.17

Molecular interactions of human Exo1 with DNA. Nucleic Acids Res (2002) 1.16

Telomere repeat binding factor 2 interacts with base excision repair proteins and stimulates DNA synthesis by DNA polymerase beta. Cancer Res (2006) 1.15

Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor. Prostate (2013) 1.15

Regulation of WRN helicase activity in human base excision repair. J Biol Chem (2004) 1.15

Hyperpolarized 13C-pyruvate magnetic resonance reveals rapid lactate export in metastatic renal cell carcinomas. Cancer Res (2012) 1.13

Inhibition of Ape1 nuclease activity by lead, iron, and cadmium. Environ Health Perspect (2004) 1.13

(1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: a novel class of potent MSK-1-inhibitors. Bioorg Med Chem Lett (2005) 1.12

Human abasic endonuclease action on multilesion abasic clusters: implications for radiation-induced biological damage. Nucleic Acids Res (2008) 1.12

The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett (2005) 1.07

XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes. J Exp Med (2011) 1.06

Intrusion of a DNA repair protein in the RNome world: is this the beginning of a new era? Mol Cell Biol (2009) 1.05

XRCC1 coordinates disparate responses and multiprotein repair complexes depending on the nature and context of the DNA damage. Environ Mol Mutagen (2011) 1.05

Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors. Int J Cancer (2012) 1.04

A quantitative model of human DNA base excision repair. I. Mechanistic insights. Nucleic Acids Res (2002) 1.04

Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population. Nucleic Acids Res (2010) 1.04

The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains. ACS Chem Biol (2013) 1.04

Human AP endonuclease (APE1) demonstrates endonucleolytic activity against AP sites in single-stranded DNA. DNA Repair (Amst) (2004) 1.02

A real-time fluorescence method for enzymatic characterization of specialized human DNA polymerases. Nucleic Acids Res (2009) 1.00

XRCC1 and DNA polymerase beta interaction contributes to cellular alkylating-agent resistance and single-strand break repair. J Cell Biochem (2005) 0.99

XRCC1 down-regulation in human cells leads to DNA-damaging agent hypersensitivity, elevated sister chromatid exchange, and reduced survival of BRCA2 mutant cells. Environ Mol Mutagen (2007) 0.98

Modulation of DNA base excision repair during neuronal differentiation. Neurobiol Aging (2013) 0.97

Direct interaction between XRCC1 and UNG2 facilitates rapid repair of uracil in DNA by XRCC1 complexes. DNA Repair (Amst) (2010) 0.96

Human macrophage migration inhibitory factor: a proven immunomodulatory cytokine? J Biol Chem (2006) 0.96

Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs. Bioorg Med Chem Lett (2006) 0.96

Repair of persistent strand breaks in the mitochondrial genome. Mech Ageing Dev (2011) 0.96

Neil1 is a genetic modifier of somatic and germline CAG trinucleotide repeat instability in R6/1 mice. Hum Mol Genet (2012) 0.96

Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation. Nucleic Acids Res (2012) 0.94

XRCC1 protects against the lethality of induced oxidative DNA damage in nondividing neural cells. Nucleic Acids Res (2008) 0.94

WRN exonuclease activity is blocked by DNA termini harboring 3' obstructive groups. Mech Ageing Dev (2006) 0.94

XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility. Nucleic Acids Res (2011) 0.94

Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem (2012) 0.93

The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency. Mech Ageing Dev (2011) 0.93

Nucleotide sequence and DNA secondary structure, as well as replication protein A, modulate the single-stranded abasic endonuclease activity of APE1. J Biol Chem (2005) 0.92

Human RECQL5 participates in the removal of endogenous DNA damage. Mol Biol Cell (2012) 0.92

The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1. DNA Repair (Amst) (2012) 0.92

Hyperpolarized [1-13C]dehydroascorbate MR spectroscopy in a murine model of prostate cancer: comparison with 18F-FDG PET. J Nucl Med (2013) 0.91

Disparity between DNA base excision repair in yeast and mammals: translational implications. Cancer Res (2003) 0.91

The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats. Biochemistry (2012) 0.91

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine. Magn Reson Imaging (2011) 0.91

Base excision repair in the mammalian brain: implication for age related neurodegeneration. Mech Ageing Dev (2013) 0.90

Rearrangement strategy for the synthesis of 2-aminoanilines. Org Lett (2010) 0.90

Diffusion MR of hyperpolarized 13C molecules in solution. Analyst (2013) 0.90

Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. PLoS One (2012) 0.90

Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients. Mech Ageing Dev (2004) 0.90

Validity of protein-osmolality versus protein-creatinine ratios in the estimation of quantitative proteinuria from random samples of urine in children. Am J Kidney Dis (2003) 0.90

Potential role of 18fluorodeoxyglucose-positron emission tomography/computed tomography in differentiating benign neurofibroma from malignant peripheral nerve sheath tumor associated with neurofibromatosis 1. Neurosurgery (2009) 0.89

Nucleic acid binding activity of human Cockayne syndrome B protein and identification of Ca(2+) as a novel metal cofactor. J Mol Biol (2009) 0.89

Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity. Nucleic Acids Res (2010) 0.88

Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors. J Med Chem (2015) 0.87

Enabling lead discovery for histone lysine demethylases by high-throughput RapidFire mass spectrometry. J Biomol Screen (2011) 0.87

A new in vivo screening paradigm to accelerate antimalarial drug discovery. PLoS One (2013) 0.86

DNA damage levels and biochemical repair capacities associated with XRCC1 deficiency. Biochemistry (2005) 0.86

S-glutathionylation of cysteine 99 in the APE1 protein impairs abasic endonuclease activity. J Mol Biol (2011) 0.86

Investigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1. J Mol Biol (2003) 0.86