Now showing items 1-20 of 60

    • Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes 

      Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, M; Palmer, Michelle; Shamji, Alykhan Farid; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.; Brady, Linda S.; Driscoll, Jamie; Li, Ingrid Y.; Loomis, Carson R.; Margolis, Ronald N.; Michelotti, Enrique; Perry, Mary E.; Pillai, Ajay; Yao, Yong (Elsevier BV, 2015)
      Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the ...
    • Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast 

      de Bivort, Benjamin Lovegren; Perlstein, Ethan O.; Kunes, Samuel M.; Schreiber, Stuart L. (Springer-Verlag, 2009)
      The metabolic cycle of Saccharomyces cerevisiae consists of alternating oxidative (respiration) and reductive (glycolysis) energy-yielding reactions. The intracellular concentrations of amino acid precursors generated by ...
    • Automated Structure-Activity Relationship Mining: Connecting Chemical Structure to Biological Profiles 

      Wawer, M. J.; Jaramillo, D. E.; Dan ik, V.; Fass, D. M.; Haggarty, Stephen John; Shamji, A. F.; Wagner, B. K.; Schreiber, Stuart L.; Clemons, P. A. (SAGE Publications, 2014)
      Understanding the structure–activity relationships (SARs) of small molecules is important for developing probes and novel therapeutic agents in chemical biology and drug discovery. Increasingly, multiplexed small-molecule ...
    • ChemBank: A Small-Molecule Screening and Cheminformatics Resource Database 

      Seiler, Kathleen Petri; George, Gregory A.; Happ, Mary Pat; Bodycombe, Nicole E.; Carrinski, Hyman A.; Norton, Stephanie; Brudz, Steve; Serrano, Martin; Ferraiolo, Paul; Tolliday, Nicola J.; Clemons, Paul A.; Sullivan, John P.; Muhlich, Jeremy; Schreiber, Stuart L. (Oxford University Press, 2008)
      ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. ...
    • Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease 

      Bradner, James Elliott; Mak, Raymond Heungwing; Tanguturi, Shyam Kumar; Mazitschek, Ralph; Haggarty, Stephen John; Ross, Kenneth N; Chang, Cindy Y.; Bosco, Jocelyn; West, Nathan; Morse, Elizabeth; Lin, Katherine; Shen, John Paul; Kwiatkowski, Nicholas Paul; Gheldof, Nele; Dekker, Job; DeAngelo, Daniel J.; Carr, Steven A.; Schreiber, Stuart L.; Golub, Todd Robert; Ebert, Benjamin L. (Proceedings of the National Academy of Sciences, 2010)
      The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications ...
    • Copper-Mediated Amidation of Heterocyclic and Aromatic C−H Bonds 

      Wang, Qiu; Schreiber, Stuart L. (American Chemical Society, 2009)
      A copper-mediated aerobic coupling reaction enables direct amidation of heterocycles or aromatics having weakly acidic C−H bonds with a variety of nitrogen nucleophiles. These reactions provide efficient access to many ...
    • Correlating chemical sensitivity and basal gene expression reveals mechanism of action 

      Rees, Matthew G; Seashore-Ludlow, Brinton; Cheah, Jaime H; Adams, Drew J; Price, Edmund V; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E; Jones, Victor Victor; Bodycombe, Nicole E; Soule, Christian K; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dancík, Vlado; Haber, Daniel A; Clish, Clary B; Bittker, Joshua A; Palmer, Michelle; Wagner, Bridget K; Clemons, Paul A; Shamji, Alykhan Farid; Schreiber, Stuart L. (Springer Nature, 2015)
      Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that ...
    • Development and Validation of a Novel Leishmania donovani Screening Cascade for High-Throughput Screening Using a Novel Axenic Assay with High Predictivity of Leishmanicidal Intracellular Activity 

      Nühs, Andrea; De Rycker, Manu; Manthri, Sujatha; Comer, Eamon; Scherer, Christina A.; Schreiber, Stuart L.; Ioset, Jean-Robert; Gray, David Michael (Public Library of Science (PLoS), 2015)
      Visceral leishmaniasis is an important parasitic disease of the developing world with a limited arsenal of drugs available for treatment. The existing drugs have significant deficiencies so there is an urgent need for new ...
    • Development and Validation of a T7 Based Linear Amplification for Genomic DNA 

      Liu, Chih Long; Schreiber, Stuart L.; Bernstein, Bradley E. (BioMed Central, 2003)
      Background: Genomic maps of transcription factor binding sites and histone modification patterns provide unique insight into the nature of gene regulatory networks and chromatin structure. These systematic studies use ...
    • Discovery and Characterization of Novel smORF-Encoded Polypeptides (SEPs) 

      Ma, Jiao (2016-01-04)
      Peptides and small proteins have essential physiological roles including metabolism (insulin), sleep (orexin), and stress (corticotropin-releasing hormone). Recent exploration of the human genome and proteome has revealed ...
    • Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation at the PAR1 Receptor 

      Dockendorff, Chris; VerPlank, Lynn; Dilks, James R.; Gunnink, Susanna F.; Palmer, Michelle; MacPherson, Lawrence; Aisiku, Omozuanvbo Reginald; Smith, Daniel A.; Dowal, Louisa; Schreiber, Stuart L.; Flaumenhaft, Robert C.; Negri, Joseph Michael (American Chemical Society, 2012)
      A high-throughput screen of the NIH-MLSMR compound collection, along with a series of secondary assays to identify potential targets of hit compounds, previously identified a 1,3-diaminobenzene scaffold that targets ...
    • Discovery of a Small-Molecule Probe for V-ATPase Function 

      Aldrich, Leslie N.; Kuo, Szu-Yu; Castoreno, Adam B.; Goel, Gautam; Kuballa, Petric; Rees, Matthew G.; Seashore-Ludlow, Brinton A.; Cheah, Jaime H.; Latorre, Isabel J.; Schreiber, Stuart L.; Shamji, Alykhan F.; Xavier, Ramnik J. (American Chemical Society, 2015)
      Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been ...
    • Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death 

      Adams, Drew J.; Boskovic, Zarko; Theriault, Jimmy R.; Wang, Alex J.; Stern, Andrew M.; Wagner, Bridget K.; Shamji, Alykhan Farid; Schreiber, Stuart L. (American Chemical Society, 2013)
      Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer ...
    • Discovery of Small-Molecule Modulators of the Sonic Hedgehog Pathway 

      Schaefer, Giannina I.; Perez, José R.; Duvall, Jeremy R.; Stanton, Benjamin Z.; Shamji, Alykhan F.; Schreiber, Stuart L. (American Chemical Society, 2013)
      The Hedgehog signaling pathway is involved in the development of multicellular organisms and, when deregulated, can contribute to certain cancers, among other diseases. The molecular characterization of the pathway, which ...
    • Disease Allele-Dependent Small-Molecule Sensitivities in Blood Cells from Monogenic Diabetes 

      Shaw, Stanley Yang; Blodgett, David M.; Ma, Maggie S.; Westly, Elizabeth C.; Clemons, Paul A.; Subramanian, Aravind; Schreiber, Stuart L. (Proceedings of the National Academy of Sciences, 2010)
      Even as genetic studies identify alleles that influence human disease susceptibility, it remains challenging to understand their functional significance and how they contribute to disease phenotypes. Here, we describe an ...
    • Distinct Biological Network Properties between the Targets of Natural Products and Disease Genes 

      Dančík, Vlado; Seiler, Kathleen Petri; Young, Damian W.; Schreiber, Stuart L.; Clemons, Paul A. (American Chemical Society, 2010)
      We show that natural products target proteins with a high number of protein−protein functional interactions (high biological network connectivity) and that these protein targets have higher network connectivity than disease ...
    • Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway 

      Gray, B. Lawrence; Wang, Xiang; Brown, Walter C.; Kuai, Letian; Schreiber, Stuart L. (American Chemical Society, 2008)
      Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high ...
    • Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria 

      Mulrooney, Carol; Austin, Christopher P.; Beaudoin, Jennifer A.; Cheng, Ken Chih-Chien; Comer, Eamon; Dandapani, Sivaraman; Dick, Justin; Duvall, Jeremy R.; Ekland, Eric H.; Fidock, David A.; Guha, Rajarshi; Hinkson, Paul; Kramer, Martin; Masi, Daniela; Marcaurelle, Lisa A.; Su, Xin-Zhuan; Weïwer, Michel; Xia, Menghang; Yuan, Jing; Zhao, Jinghua; Palmer, Michelle; Munoz, Benito; Heidebrecht, Richard W; Barker, Robert Howard; Fitzgerald, Mark E.; Foley, Michael Raymond; Lukens, Amanda Kathleen; Thomas, Craig J.; Wiegand, Roger C.; Wirth, Dyann Fergus; Schreiber, Stuart L. (AmericanChemical Society, 2011)
      Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis ...
    • Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents 

      Comer, Eamon; Beaudoin, Jennifer A.; Kato, Nobutaka; Fitzgerald, Mark E.; Heidebrecht, Richard W.; Lee, Maurice duPont; Masi, Daniela; Mercier, Marion; Mulrooney, Carol; Muncipinto, Giovanni; Rowley, Ann; Crespo-Llado, Keila; Serrano, Adelfa E.; Lukens, Amanda K.; Wiegand, Roger C.; Wirth, Dyann F.; Palmer, Michelle A.; Foley, Michael A.; Munoz, Benito; Scherer, Christina A.; Duvall, Jeremy R.; Schreiber, Stuart L. (American Chemical Society, 2014)
      Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic ...
    • Empirical Bayes Analysis of Quantitative Proteomics Experiments 

      Margolin, Adam A.; Ong, Shao-En; Schenone, Monica; Gould, Robert; Schreiber, Stuart L.; Carr, Steven A.; Golub, Todd R. (Public Library of Science, 2009)
      Background: Advances in mass spectrometry-based proteomics have enabled the incorporation of proteomic data into systems approaches to biology. However, development of analytical methods has lagged behind. Here we describe ...