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. 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...
  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. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. Metabolically stable dibenzo[b,e]oxepin-11(6H)-ones as highly selective p38 MAP kinase inhibitors: optimizing anti-cytokine activity in human whole blood.

    Journal of medicinal and pharmaceutical chemistry 56(21):8561 (2013) PMID 24131218

    Five series of metabolically stable disubstituted dibenzo[b,e]oxepin-11(6H)-ones were synthesized and tested in a p38α enzyme assay for their inhibition of tumor necrosis factor-α (TNF-α) release in human whole blood. Compared to the monosubstituted dibenzo[b,e]oxepin-11(6H)-one derivatives, it ...
  14. Metabolically stable dibenzo[b,e]oxepin-11(6H)-ones as highly selective p38 MAP kinase inhibitors: optimizing anti-cytokine activity in human whole blood.

    Journal of medicinal and pharmaceutical chemistry 56(21):8561 (2013) PMID 24131218

    Five series of metabolically stable disubstituted dibenzo[b,e]oxepin-11(6H)-ones were synthesized and tested in a p38α enzyme assay for their inhibition of tumor necrosis factor-α (TNF-α) release in human whole blood. Compared to the monosubstituted dibenzo[b,e]oxepin-11(6H)-one derivatives, it ...
  15. Targeting gain of function and resistance mutations in Abl and KIT by hybrid compound design.

    Journal of medicinal and pharmaceutical chemistry 56(14):5757 (2013) PMID 23773153

    Mutations in the catalytic domain at the gatekeeper position represent the most prominent drug-resistant variants of kinases and significantly impair the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular and atomic levels will aid in the desi...
  16. Targeting gain of function and resistance mutations in Abl and KIT by hybrid compound design.

    Journal of medicinal and pharmaceutical chemistry 56(14):5757 (2013) PMID 23773153

    Mutations in the catalytic domain at the gatekeeper position represent the most prominent drug-resistant variants of kinases and significantly impair the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular and atomic levels will aid in the desi...
  17. De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments.

    ACS Chemical Biology 8(5):1044 (2013) PMID 23534475 PMCID PMC3833278

    Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discove...
  18. De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments.

    ACS Chemical Biology 8(5):1044 (2013) PMID 23534475 PMCID PMC3833278

    Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discove...
  19. A framework for identification of actionable cancer genome dependencies in small cell lung cancer.

    PNAS 109(42):17034 (2012) PMID 23035247 PMCID PMC3479457

    Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of SCLC patients is devastating and no biologically targeted therapeutics are active in this tumor type. To develop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic ...
  20. A framework for identification of actionable cancer genome dependencies in small cell lung cancer.

    PNAS 109(42):17034 (2012) PMID 23035247 PMCID PMC3479457

    Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of SCLC patients is devastating and no biologically targeted therapeutics are active in this tumor type. To develop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic ...