Fragment-based lead discovery: a chemical update.

[1]  Maurizio Pellecchia,et al.  Structure–activity relationships by interligand NOE-based design and synthesis of antiapoptotic compounds targeting Bid , 2006, Proceedings of the National Academy of Sciences.

[2]  Mark Whittaker,et al.  Fragment screening by biochemical assay , 2006, Expert opinion on drug discovery.

[3]  György M Keseru,et al.  Hit discovery and hit-to-lead approaches. , 2006, Drug discovery today.

[4]  T. Blundell,et al.  Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods. , 2006, Journal of medicinal chemistry.

[5]  Eric F. Johnson,et al.  Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors. , 2006, Journal of medicinal chemistry.

[6]  W. Pitt,et al.  Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships. , 2006, Bioorganic & medicinal chemistry letters.

[7]  W. Pitt,et al.  Low molecular weight indole fragments as IMPDH inhibitors. , 2006, Bioorganic & medicinal chemistry letters.

[8]  Paul J Edwards,et al.  The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors. , 2006, Bioorganic & medicinal chemistry letters.

[9]  D. Christianson,et al.  Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity. , 2006, Journal of the American Chemical Society.

[10]  Christian Rummey,et al.  In silico fragment-based discovery of DPP-IV S1 pocket binders. , 2006, Bioorganic & medicinal chemistry letters.

[11]  William Lindstrom,et al.  Inhibitors of HIV-1 protease by using in situ click chemistry. , 2006, Angewandte Chemie.

[12]  Joni W. Lam,et al.  Tethering identifies fragment that yields potent inhibitors of human caspase-1. , 2006, Bioorganic & medicinal chemistry letters.

[13]  P. Hajduk,et al.  Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and parallel synthesis. , 2006, Journal of medicinal chemistry.

[14]  Gianni Chessari,et al.  Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors. , 2006, Journal of medicinal chemistry.

[15]  A. Petros,et al.  Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2 family proteins with chemopotentiation activity in vitro and in vivo. , 2006, Journal of medicinal chemistry.

[16]  P. Hajduk,et al.  Predicting protein druggability. , 2005, Drug discovery today.

[17]  Simona Golic Grdadolnik,et al.  In silico fragment-based discovery of indolin-2-one analogues as potent DNA gyrase inhibitors. , 2005, Bioorganic & medicinal chemistry letters.

[18]  D. Poirier,et al.  Estradiol-adenosine hybrid compounds designed to inhibit type 1 17beta-hydroxysteroid dehydrogenase. , 2005, Journal of medicinal chemistry.

[19]  Christopher W Murray,et al.  Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation. , 2005, Journal of medicinal chemistry.

[20]  Gergely M Makara,et al.  Improving success rates for lead generation using affinity binding technologies , 2005, Current Opinion in Biotechnology.

[21]  Rangarajan Sampath,et al.  SAR by MS: discovery of a new class of RNA-binding small molecules for the hepatitis C virus: internal ribosome entry site IIA subdomain. , 2005, Journal of medicinal chemistry.

[22]  J. Ellman,et al.  Substrate activity screening: a fragment-based method for the rapid identification of nonpeptidic protease inhibitors. , 2005, Journal of the American Chemical Society.

[23]  F. J. Luque,et al.  Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease. , 2005, Journal of medicinal chemistry.

[24]  Edward R Zartler,et al.  Fragonomics: fragment-based drug discovery. , 2005, Current opinion in chemical biology.

[25]  Edgar Jacoby,et al.  Library design for fragment based screening. , 2005, Current topics in medicinal chemistry.

[26]  Christopher W Murray,et al.  Fragment-based lead discovery: leads by design. , 2005, Drug discovery today.

[27]  Dawoon Jung,et al.  Efficient synthetic inhibitors of anthrax lethal factor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Korsmeyer,et al.  An inhibitor of Bcl-2 family proteins induces regression of solid tumours , 2005, Nature.

[29]  Didier Rognan,et al.  Design of small-sized libraries by combinatorial assembly of linkers and functional groups to a given scaffold: application to the structure-based optimization of a phosphodiesterase 4 inhibitor. , 2005, Journal of medicinal chemistry.

[30]  Joni W. Lam,et al.  Structural analysis of caspase-1 inhibitors derived from Tethering. , 2005, Acta crystallographica. Section F, Structural biology and crystallization communications.

[31]  Zoran Radić,et al.  In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors. , 2005, Journal of the American Chemical Society.

[32]  J. T. Metz,et al.  Ligand efficiency indices as guideposts for drug discovery. , 2005, Drug discovery today.

[33]  H. Jhoti,et al.  The Discovery of Novel Protein Kinase Inhibitors by Using Fragment‐Based High‐Throughput X‐ray Crystallography , 2005, Chembiochem : a European journal of chemical biology.

[34]  Jean-Louis Reymond,et al.  Virtual exploration of the small-molecule chemical universe below 160 Daltons. , 2005, Angewandte Chemie.

[35]  P. Hajduk,et al.  Druggability indices for protein targets derived from NMR-based screening data. , 2005, Journal of medicinal chemistry.

[36]  Andrea Madami,et al.  Generation of a new class of hNK(2) receptor ligands using the 'fragment approach'. , 2005, Bioorganic & medicinal chemistry letters.

[37]  H. Jhoti,et al.  A new school for screening , 2005, Nature Biotechnology.

[38]  Kam Y. J. Zhang,et al.  A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design , 2005, Nature Biotechnology.

[39]  Christopher W Murray,et al.  Fragment-based lead discovery using X-ray crystallography. , 2005, Journal of medicinal chemistry.

[40]  Hualiang Jiang,et al.  Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors. , 2005, Journal of medicinal chemistry.

[41]  Dawoon Jung,et al.  NMR-based techniques in the hit identification and optimisation processes , 2004, Expert opinion on therapeutic targets.

[42]  Joel L Sussman,et al.  The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. , 2004, Journal of the American Chemical Society.

[43]  Zoran Radić,et al.  In situ click chemistry: enzyme inhibitors made to their own specifications. , 2004, Journal of the American Chemical Society.

[44]  D. Erlanson,et al.  Tethering in early target assessment , 2004 .

[45]  Daniel A Erlanson,et al.  Making drugs on proteins: site-directed ligand discovery for fragment-based lead assembly. , 2004, Current opinion in chemical biology.

[46]  M. Congreve,et al.  Fragment-based lead discovery , 2004, Nature Reviews Drug Discovery.

[47]  Jeffrey W. Peng,et al.  Theory and applications of NMR-based screening in pharmaceutical research. , 2004, Chemical reviews.

[48]  M. Verdonk,et al.  Structure-guided fragment screening for lead discovery. , 2004, Current opinion in drug discovery & development.

[49]  T. O'Brien,et al.  Fragment-based drug discovery. , 2004, Journal of medicinal chemistry.

[50]  Tudor I. Oprea,et al.  Pursuing the leadlikeness concept in pharmaceutical research. , 2004, Current opinion in chemical biology.

[51]  A. Hopkins,et al.  Ligand efficiency: a useful metric for lead selection. , 2004, Drug discovery today.

[52]  Daniel A Erlanson,et al.  Tethering: fragment-based drug discovery. , 2004, Annual review of biophysics and biomolecular structure.

[53]  M. McCoy,et al.  Non-peptidic small-molecule inhibitors of the single-chain hepatitis C virus NS3 protease/NS4A cofactor complex discovered by structure-based NMR screening. , 2004, Journal of medicinal chemistry.

[54]  Christoph E. Dumelin,et al.  Encoded self-assembling chemical libraries , 2004, Nature Biotechnology.

[55]  Chi‐Huey Wong,et al.  Dimeric aminoglycosides as antibiotics. , 2004, Angewandte Chemie.

[56]  D. Fattori,et al.  Molecular recognition: the fragment approach in lead generation. , 2004, Drug discovery today.

[57]  A. Gill,et al.  New lead generation strategies for protein kinase inhibitors - fragment based screening approaches. , 2004, Mini reviews in medicinal chemistry.

[58]  Jean M. Severin,et al.  Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization. , 2004, Journal of medicinal chemistry.

[59]  Zoran Radić,et al.  Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Maurizio Pellecchia,et al.  Systems-based design of bi-ligand inhibitors of oxidoreductases: filling the chemical proteomic toolbox. , 2004, Chemistry & biology.

[61]  Jeffrey W. Peng,et al.  Leveraging structural approaches: applications of NMR-based screening and X-ray crystallography for inhibitor design. , 2004, Journal of synchrotron radiation.

[62]  Chi-Huey Wong,et al.  In situ click chemistry: enzyme-generated inhibitors of carbonic anhydrase II. , 2004, Angewandte Chemie.

[63]  A. Sharff,et al.  High-throughput crystallography to enhance drug discovery. , 2003, Current opinion in chemical biology.

[64]  Neera Borkakoti,et al.  Discovery of novel low molecular weight inhibitors of IMPDH via virtual needle screening. , 2003, Bioorganic & medicinal chemistry letters.

[65]  W. Delano,et al.  In situ assembly of enzyme inhibitors using extended tethering , 2003, Nature Biotechnology.

[66]  H. Jhoti,et al.  Structure-based screening of low-affinity compounds. , 2002, Drug discovery today.

[67]  P. Taylor,et al.  Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. , 2002, Angewandte Chemie.

[68]  Harren Jhoti,et al.  High-throughput crystallography for lead discovery in drug design , 2002, Nature Reviews Drug Discovery.

[69]  Andrew R. Leach,et al.  Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery , 2001, J. Chem. Inf. Comput. Sci..

[70]  Vicki L. Nienaber,et al.  Discovering novel ligands for macromolecules using X-ray crystallographic screening , 2000, Nature Biotechnology.

[71]  Tudor I. Oprea,et al.  The Design of Leadlike Combinatorial Libraries. , 1999, Angewandte Chemie.

[72]  I. Kuntz,et al.  The maximal affinity of ligands. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[73]  P. Hajduk,et al.  Discovering High-Affinity Ligands for Proteins: SAR by NMR , 1996, Science.

[74]  W. Guida,et al.  The art and practice of structure‐based drug design: A molecular modeling perspective , 1996, Medicinal research reviews.

[75]  P. Andrews,et al.  Functional group contributions to drug-receptor interactions. , 1984, Journal of medicinal chemistry.

[76]  W. Jencks,et al.  On the attribution and additivity of binding energies. , 1981, Proceedings of the National Academy of Sciences of the United States of America.