1. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  2. Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR.

    Bioorganic & Medicinal Chemistry 23(12):2767 (2015) PMID 25975640

    The clinical success of covalent kinase inhibitors in the treatment of EGFR-dependent non-small cell lung cancer (NSCLC) has rejuvenated the appreciation of reactive small molecules. Acquired drug resistance against first-line EGFR inhibitors remains the major bottleneck in NSCLC and is currentl...
  3. Monitoring ligand-induced conformational changes for the identification of estrogen receptor agonists and antagonists.

    Angewandte Chemie. International edition in Eng... 54(14):4379 (2015) PMID 25664555

    Nuclear receptors are transcription factors that are important targets for current drug discovery efforts as they play a role in many pathological processes. Their activity can be regulated by small molecules like hormones and drugs that can have agonistic or antagonistic functions. These ligand...
  4. Identification and Further Development of Potent TBK1 Inhibitors.

    ACS Chemical Biology 10(1):289 (2015) PMID 25540906

    The cytosolic Ser/Thr kinase TBK1 was discovered to be an essential element in the mediation of signals that lead to tumor migration and progression. These findings meet the need for the identification of novel tool compounds and potential therapeutics to gain deeper insights into TBK1 related s...
  5. Special issue focused on two areas pertinent to chemical biology: post-translational modifications and new frontiers on kinases.

    ACS Chemical Biology 10(1):1 (2015) PMID 25591742

  6. Special issue focused on two areas pertinent to chemical biology: post-translational modifications and new frontiers on kinases.

    ACS Chemical Biology 10(1):1 (2015) PMID 25591742

  7. Discovery of inter-domain stabilizers-a novel assay system for allosteric akt inhibitors.

    ACS Chemical Biology 10(1):279 (2015) PMID 24959717

    In addition to the catalytically active kinase domain, most kinases feature regulatory domains that govern their activity. Modulating and interfering with these interdomain interactions presents a major opportunity for understanding biological systems and developing novel therapeutics. Therefore...
  8. Identification and further development of potent TBK1 inhibitors.

    ACS Chemical Biology 10(1):289 (2015) PMID 25540906

    The cytosolic Ser/Thr kinase TBK1 was discovered to be an essential element in the mediation of signals that lead to tumor migration and progression. These findings meet the need for the identification of novel tool compounds and potential therapeutics to gain deeper insights into TBK1 related s...
  9. Identification and further development of potent TBK1 inhibitors.

    ACS Chemical Biology 10(1):289 (2015) PMID 25540906

    The cytosolic Ser/Thr kinase TBK1 was discovered to be an essential element in the mediation of signals that lead to tumor migration and progression. These findings meet the need for the identification of novel tool compounds and potential therapeutics to gain deeper insights into TBK1 related s...
  10. Discovery of inter-domain stabilizers-a novel assay system for allosteric akt inhibitors.

    ACS Chemical Biology 10(1):279 (2015) PMID 24959717

    In addition to the catalytically active kinase domain, most kinases feature regulatory domains that govern their activity. Modulating and interfering with these interdomain interactions presents a major opportunity for understanding biological systems and developing novel therapeutics. Therefore...
  11. Discovery of inter-domain stabilizers-a novel assay system for allosteric akt inhibitors.

    ACS Chemical Biology 10(1):279 (2015) PMID 24959717

    In addition to the catalytically active kinase domain, most kinases feature regulatory domains that govern their activity. Modulating and interfering with these interdomain interactions presents a major opportunity for understanding biological systems and developing novel therapeutics. Therefore...
  12. Combining X-ray Crystallography and Molecular Modeling toward the Optimization of Pyrazolo[3,4-d]pyrimidines as Potent c-Src Inhibitors Active in Vivo against Neuroblastoma.

    Journal of medicinal and pharmaceutical chemistry 58(1):347 (2015) PMID 25469771

    c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimidine 3 was reported as a dual c-Src/Abl i...
  13. Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo[3,4-d]pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma.

    Journal of medicinal and pharmaceutical chemistry 58(1):347 (2015) PMID 25469771

    c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimidine 3 was reported as a dual c-Src/Abl i...
  14. Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo[3,4-d]pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma.

    Journal of medicinal and pharmaceutical chemistry 58(1):347 (2015) PMID 25469771

    c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimidine 3 was reported as a dual c-Src/Abl i...
  15. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues.

    Biological Chemistry 395(7-8):891 (2014) PMID 25003390

    A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a s...
  16. Identification of type II and III DDR2 inhibitors.

    Journal of medicinal and pharmaceutical chemistry 57(10):4252 (2014) PMID 24754677

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recent...
  17. Identification of type II and III DDR2 inhibitors.

    Journal of medicinal and pharmaceutical chemistry 57(10):4252 (2014) PMID 24754677

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recent...
  18. A special thematic compilation/special issue crossover with Biochemistry, Journal of Medicinal Chemistry, and ACS Medicinal Chemistry Letters focused on kinases.

    ACS Chemical Biology 9(3):579 (2014) PMID 24650390

  19. A special thematic compilation/special issue crossover with Biochemistry, Journal of Medicinal Chemistry, and ACS Medicinal Chemistry Letters focused on kinases.

    ACS Chemical Biology 9(3):579 (2014) PMID 24650390

  20. Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified FGFR1 in lung cancer.

    Cancer Discovery 4(2):246 (2014) PMID 24302556

    The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other re...