Search Results - "Doak, Bradley C"

Impact of Dynamically Exposed Polarity on Permeability and Solubility of Chameleonic Drugs Beyond the Rule of 5 by Rossi Sebastiano, Matteo, Doak, Bradley C, Backlund, Maria, Poongavanam, Vasanthanathan, Over, Björn, Ermondi, Giuseppe, Caron, Giulia, Matsson, Pär, Kihlberg, Jan

“…Conformational flexibility has been proposed to significantly affect drug properties outside rule-of-5 (Ro5) chemical space. Here, we investigated the…”
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The ways and means of fragment-based drug design by Doak, Bradley C, Norton, Raymond S, Scanlon, Martin J

“…Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to…”
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Structural and conformational determinants of macrocycle cell permeability by Over, Björn, Matsson, Pär, Tyrchan, Christian, Artursson, Per, Doak, Bradley C, Foley, Michael A, Hilgendorf, Constanze, Johnston, Stephen E, Lee, Maurice D, Lewis, Richard J, McCarren, Patrick, Muncipinto, Giovanni, Norinder, Ulf, Perry, Matthew W D, Duvall, Jeremy R, Kihlberg, Jan

“…Detailed computational and structural analysis of a large data set of non-peptidic macrocycles revealed particular functional groups, substituents and…”
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Methyl probes in proteins for determining ligand binding mode in weak protein–ligand complexes by Mohanty, Biswaranjan, Orts, Julien, Wang, Geqing, Nebl, Stefan, Alwan, Wesam S., Doak, Bradley C., Williams, Martin L., Heras, Begoña, Mobli, Mehdi, Scanlon, Martin J.

“…Structures of protein–ligand complexes provide critical information for drug design. Most protein–ligand complex structures are determined using X-ray…”
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Application of Fragment-Based Screening to the Design of Inhibitors of Escherichia coli DsbA by Adams, Luke A., Sharma, Pooja, Mohanty, Biswaranjan, Ilyichova, Olga V., Mulcair, Mark D., Williams, Martin L., Gleeson, Ellen C., Totsika, Makrina, Doak, Bradley C., Caria, Sofia, Rimmer, Kieran, Horne, James, Shouldice, Stephen R., Vazirani, Mansha, Headey, Stephen J., Plumb, Brent R., Martin, Jennifer L., Heras, Begoña, Simpson, Jamie S., Scanlon, Martin J.

“…The thiol‐disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram‐negative bacteria. DsbA substrates include…”
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Fragment screening libraries for the identification of protein hot spots and their minimal binding pharmacophores by Whitehouse, Rebecca L, Alwan, Wesam S, Ilyichova, Olga V, Taylor, Ashley J, Chandrashekaran, Indu R, Mohanty, Biswaranjan, Doak, Bradley C, Scanlon, Martin J

“…Fragment-based drug design relies heavily on structural information for the elaboration and optimisation of hits. The ability to identify neighbouring binding…”
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How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets by Doak, Bradley C, Zheng, Jie, Dobritzsch, Doreen, Kihlberg, Jan

“…To improve discovery of drugs for difficult targets, the opportunities of chemical space beyond the rule of 5 (bRo5) were examined by retrospective analysis of…”
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Opportunities and guidelines for discovery of orally absorbed drugs in beyond rule of 5 space by Poongavanam, Vasanthanathan, Doak, Bradley C., Kihlberg, Jan

“…Recent years have seen a dramatic increase in the number of drugs approved in chemical space outside of Lipinski’s rule of 5, that is in what has been termed…”
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Cell permeability beyond the rule of 5 by Matsson, Pär, Doak, Bradley C., Over, Björn, Kihlberg, Jan

“…Drug discovery for difficult targets that have large and flat binding sites is often better suited to compounds beyond the “rule of 5” (bRo5). However, such…”
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Drug discovery beyond the rule of 5 - Opportunities and challenges by Doak, Bradley C, Kihlberg, Jan

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Drug Syntheses Beyond the Rule of 5 by Tyagi, Mohit, Begnini, Fabio, Poongavanam, Vasanthanathan, Doak, Bradley C., Kihlberg, Jan

“…Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral…”
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Cyclophilin Succumbs to a Macrocyclic Chameleon by Doak, Bradley C, Kihlberg, Jan

“…Targets that have large and groove-shaped binding sites, such as cyclophilin, are difficult to drug with small molecules. Macrocycles of natural product origin…”
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Frontispiece: Drug Syntheses Beyond the Rule of 5 by Tyagi, Mohit, Begnini, Fabio, Poongavanam, Vasanthanathan, Doak, Bradley C., Kihlberg, Jan

“…Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites, with most of those approved since 1990 belonging to…”
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Rapid Elaboration of Fragments into Leads Applied to Bromodomain‑3 Extra-Terminal Domain by Adams, Luke A., Wilkinson-White, Lorna E., Gunzburg, Menachem J., Headey, Stephen J., Mohanty, Biswaranjan, Scanlon, Martin J., Capuano, Ben, Mackay, Joel P., Doak, Bradley C.

“…The development of low-affinity fragment hits into higher-affinity leads is a major hurdle in fragment-based drug design. Here, we demonstrate the Rapid…”
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Rapid Elaboration of Fragments into Leads by X‑ray Crystallographic Screening of Parallel Chemical Libraries (REFiLX) by Bentley, Matthew R, Ilyichova, Olga V, Wang, Geqing, Williams, Martin L, Sharma, Gaurav, Alwan, Wesam S, Whitehouse, Rebecca L, Mohanty, Biswaranjan, Scammells, Peter J, Heras, Begoña, Martin, Jennifer L, Totsika, Makrina, Capuano, Ben, Doak, Bradley C, Scanlon, Martin J

“…A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low…”
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Fluoromethylketone‐Fragment Conjugates Designed as Covalent Modifiers of EcDsbA are Atypical Substrates by Doak, Bradley C., Whitehouse, Rebecca L., Rimmer, Kieran, Williams, Martin, Heras, Begoña, Caria, Sofia, Ilyichova, Olga, Vazirani, Mansha, Mohanty, Biswaranjan, Harper, Jason B., Scanlon, Martin J., Simpson, Jamie S.

“…Disulfide bond protein A (DsbA) is an oxidoreductase enzyme that catalyzes the formation of disulfide bonds in Gram‐negative bacteria. In Escherichia coli,…”
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Multiplexed Native Mass Spectrometry Determination of Ligand Selectivity for Fatty Acid-Binding Proteins by Phan, Michelle Q., Chandrashekaran, Indu R., Akhtar, Naureen, Konstantinidou, Evgenia, Devine, Shane M., Doak, Bradley C., Nebl, Thomas, Creek, Darren J., Scanlon, Martin J., Norton, Raymond S.

“…Although multiple approaches for characterizing protein–ligand interactions are available in target-based drug discovery, their throughput for determining…”
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Synthesis of Unsymmetrical 1,1′-Disubstituted Bis(1,2,3-triazole)s Using Monosilylbutadiynes by Doak, Bradley C., Scanlon, Martin J., Simpson, Jamie S.

“…Bis(1,2,3-triazole)s have attracted recent interest as coordinating ligands for transition metals. Here we report a rapid, modular method for the synthesis of…”
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Structural and biochemical insights into the disulfide reductase mechanism of DsbD, an essential enzyme for neisserial pathogens by Smith, Roxanne P., Mohanty, Biswaranjan, Mowlaboccus, Shakeel, Paxman, Jason J., Williams, Martin L., Headey, Stephen J., Wang, Geqing, Subedi, Pramod, Doak, Bradley C., Kahler, Charlene M., Scanlon, Martin J., Heras, Begoña

“…The worldwide incidence of neisserial infections, particularly gonococcal infections, is increasingly associated with antibiotic-resistant strains. In…”
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NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfide–dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei by Nebl, Stefan, Alwan, Wesam S., Williams, Martin L., Sharma, Gaurav, Taylor, Ashley, Doak, Bradley C., Wilde, Karyn L., McMahon, Róisín M., Halili, Maria A., Martin, Jennifer L., Capuano, Ben, Fenwick, R. Bryn, Mohanty, Biswaranjan, Scanlon, Martin J.

“…The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as ‘druggable’…”
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