1. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.

    Nature Chemical Biology 11(3):189 (2015) PMID 25622091

    PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of huma...
  2. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.

    Nature Chemical Biology 11(3):189 (2015) PMID 25622091 PMCID PMC4397581

    PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of huma...
  3. Proteomics. Tracking cancer drugs in living cells by thermal profiling of the proteome.

    Science 346(6205):1255784 (2014) PMID 25278616

    The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles d...
  4. Tracking cancer drugs in living cells by thermal profiling of the proteome.

    Science 346(6205):1255784 (2014) PMID 25278616

    The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles d...
  5. Kruidenier et al. reply.

    Nature 514(7520):E2 (2014) PMID 25279927

  6. Kruidenier et al. reply.

    Nature 514(7520):E2 (2014) PMID 25279927

  7. Kruidenier et al. reply.

    Nature 514(7520):E2 (2014) PMID 25279927

  8. Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors to endogenous repressor complexes.

    ACS Chemical Biology 9(8):1736 (2014) PMID 24877719

    Class I histone deacetylases (HDACs) are attractive drug targets in oncology and inflammation. However, the development of selective inhibitors is complicated by the characteristic that the localization, activity, and selectivity of class I HDACs are regulated by association in megadalton repres...
  9. Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors to endogenous repressor complexes.

    ACS Chemical Biology 9(8):1736 (2014) PMID 24877719

    Class I histone deacetylases (HDACs) are attractive drug targets in oncology and inflammation. However, the development of selective inhibitors is complicated by the characteristic that the localization, activity, and selectivity of class I HDACs are regulated by association in megadalton repres...
  10. Drug selectivity: Running in the family.

    Nature Chemical Biology 10(8):608 (2014) PMID 24997603

  11. Drug selectivity: Running in the family.

    Nature Chemical Biology 10(8):608 (2014) PMID 24997603

  12. The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains.

    ACS Chemical Biology 9(2):495 (2014) PMID 24533473

    A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that co...
  13. The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains.

    ACS Chemical Biology 9(2):495 (2014) PMID 24533473

    A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that co...
  14. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor.

    Journal of medicinal and pharmaceutical chemistry 56(7):3012 (2013) PMID 23473363

    Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological biotargets with possible applications for the development of novel anticancer therapeutics. A focused structure-activity relationship study was conducted based on the tankyrase inhibitor JW74 (1). Chemical analoging of 1 improved the 1,2...
  15. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor.

    Journal of medicinal and pharmaceutical chemistry 56(7):3012 (2013) PMID 23473363

    Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological biotargets with possible applications for the development of novel anticancer therapeutics. A focused structure-activity relationship study was conducted based on the tankyrase inhibitor JW74 (1). Chemical analoging of 1 improved the 1,2...
  16. Affinity profiling of the cellular kinome for the nucleotide cofactors ATP, ADP, and GTP.

    ACS Chemical Biology 8(3):599 (2013) PMID 23215245

    Most kinase inhibitor drugs target the binding site of the nucleotide cosubstrate ATP. The high intracellular concentration of ATP can strongly affect inhibitor potency and selectivity depending on the affinity of the target kinase for ATP. Here we used a defined chemoproteomics system based on ...
  17. Affinity profiling of the cellular kinome for the nucleotide cofactors ATP, ADP, and GTP.

    ACS Chemical Biology 8(3):599 (2013) PMID 23215245

    Most kinase inhibitor drugs target the binding site of the nucleotide cosubstrate ATP. The high intracellular concentration of ATP can strongly affect inhibitor potency and selectivity depending on the affinity of the target kinase for ATP. Here we used a defined chemoproteomics system based on ...
  18. Affinity profiling of the cellular kinome for the nucleotide cofactors ATP, ADP, and GTP.

    ACS Chemical Biology 8(3):599 (2013) PMID 23215245

    Most kinase inhibitor drugs target the binding site of the nucleotide cosubstrate ATP. The high intracellular concentration of ATP can strongly affect inhibitor potency and selectivity depending on the affinity of the target kinase for ATP. Here we used a defined chemoproteomics system based on ...
  19. Chemical proteomic analysis reveals the drugability of the kinome of Trypanosoma brucei.

    ACS Chemical Biology 7(11):1858 (2012) PMID 22908928 PMCID PMC3621575

    The protozoan parasite Trypanosoma brucei is the causative agent of African sleeping sickness, and there is an urgent unmet need for improved treatments. Parasite protein kinases are attractive drug targets, provided that the host and parasite kinomes are sufficiently divergent to allow specific...
  20. Chemical proteomic analysis reveals the drugability of the kinome of Trypanosoma brucei.

    ACS Chemical Biology 7(11):1858 (2012) PMID 22908928 PMCID PMC3621575

    The protozoan parasite Trypanosoma brucei is the causative agent of African sleeping sickness, and there is an urgent unmet need for improved treatments. Parasite protein kinases are attractive drug targets, provided that the host and parasite kinomes are sufficiently divergent to allow specific...