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    United Kingdom

Accepting PhD Students

PhD projects

My lab is open to medicinal chemistry and biochemistry PhD studentships applications. Research fields of interest include: - small molecule inhibitors - protease chemical biology - cancer - respiratory diseases - cystic fibrosis Previous research experience is desirable although not essential.

20022019
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Research Output 2002 2019

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Article
2019
61 Downloads (Pure)

A Novel Role for Cathepsin S as a Potential Biomarker in Triple Negative Breast Cancer

Wilkinson, R., Burden, R., McDowell, S., McArt, D., McQuaid, S., Bingham, V., Williams, R., Cox, O., O'Connor, R., McCabe, N., Kennedy, R., Buckley, N. E. & Scott, C., 28 Jun 2019, In : Journal of Oncology.

Research output: Contribution to journalArticle

Open Access
File
cathepsin S
Triple Negative Breast Neoplasms
Biomarkers
Neoplasms
DNA Repair

Identification and SAR exploration of a novel series of Legumain inhibitors

Eddie, S. L., Gregson, A., Graham, E., Burton, S., Harrison, T., Burden, R., Scott, C. J., Mullan, P. B. & Williams, R., 15 Jun 2019, In : Bioorganic & Medicinal Chemistry Letters. 29, 12, p. 1546-1548 3 p.

Research output: Contribution to journalArticle

asparaginylendopeptidase
Dipeptides
Molecules
Research
Experiments
2018
1 Citation (Scopus)
25 Downloads (Pure)

Development of an advanced nanoformulation for the intracellular delivery of a caspase-3 selective activity-based probe

Cogo, F., Smyth, P., Burden, R., Longley, D. B., Williams, R., Johnston, M., Poreba, M., Rut, W., Groborz, K., Salvesen, G., Drag, M. & Scott, C. J., 13 Dec 2018, In : Nanoscale - Royal Society of Chemistry.

Research output: Contribution to journalArticle

Open Access
File
Caspase 3
Labels
Labeling
Tumors
Pharmacodynamics
2016
12 Citations (Scopus)
239 Downloads (Pure)

A bioavailable cathepsin S nitrile inhibitor abrogates tumor development

Wilkinson, R. D. A., Young, A., Burden, R. E., Williams, R. & Scott, C. J., 21 Apr 2016, In : Molecular Cancer. 15, 29, 11 p.

Research output: Contribution to journalArticle

Open Access
File
cathepsin S
Nitriles
Neoplasms
MCF-7 Cells
Apoptosis
1 Citation (Scopus)

Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

Ness, K. A., Eddie, S. L., Burton, S., Harrison, T., Mullan, P. & Williams, R., 15 Jan 2016, In : Bioorganic and Medicinal Chemistry Letters. 26, 2, p. 413-6 4 p.

Research output: Contribution to journalArticle

asparaginylendopeptidase
Molecules
20 Citations (Scopus)

Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases

Hamon, Y., Legowska, M., Hervé, V., Dallet-Choisy, S., Marchand-Adam, S., Vanderlynden, L., Demonte, M., Williams, R., Scott, C. J., Si-Tahar, M., Heuzé-Vourc'h, N., Lalmanach, G., Jenne, D. E., Lesner, A., Gauthier, F. & Korkmaz, B., 15 Apr 2016, In : The Journal of biological chemistry. 291, 16, p. 8486-99 14 p.

Research output: Contribution to journalArticle

Cathepsin C
Pulmonary diseases
Lung Diseases
Serine Proteases
Cats
2015
16 Citations (Scopus)
184 Downloads (Pure)

CCL2 is transcriptionally controlled by the lysosomal protease cathepsin S in a CD74-dependent manner

Wilkinson, R., Magorrian, S., Williams, R., Young, A., Small, D., Scott, C. & Burden, R., 22 Aug 2015, In : Oncotarget. p. 1-15 15 p.

Research output: Contribution to journalArticle

Open Access
File
cathepsin S
protease S
Neoplasms
Tumor Microenvironment
2014
7 Citations (Scopus)

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: Development of a potent and CNS penetrant [3.1.0]-based lead

Jones, C. K., Sheffler, D. J., Williams, R., Jadhav, S. B., Felts, A. S., Morrison, R. D., Niswender, C. M., Daniels, J. S. & Conn, P. J., 15 Feb 2014, In : Bioorganic and Medicinal Chemistry Letters. 24, 5, p. 1067-1070 4 p.

Research output: Contribution to journalArticle

Intellectual Property
Intellectual property
Scaffolds
Schizophrenia
Lead
3 Citations (Scopus)

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

Sheffler, D. J., Nedelovych, M. T., Williams, R., Turner, S. C., Duerk, B. B., Robbins, M. R., Jadhav, S. B., Niswender, C. M., Jones, C. K., Conn, P. J., Daniels, R. N. & Lindsley, C. W., 15 Feb 2014, In : Bioorganic and Medicinal Chemistry Letters. 24, 4, p. 1062-1066 5 p.

Research output: Contribution to journalArticle

Intellectual Property
Intellectual property
Scaffolds
piperidine
4 Citations (Scopus)

P3 SAR exploration of biphenyl carbamate based Legumain inhibitors

Higgins, C., Bouazzaoui, S., Gaddale Devanna, K., D'Costa, Z., Templeman, A., O'Rourke, M., Young, A., Scott, C., Harrison, T., Mullan, P. & Williams, R., 01 Jun 2014, In : Bioorganic and Medicinal Chemistry Letters. 24, 11, p. 2521-2524

Research output: Contribution to journalArticle

asparaginylendopeptidase
Carbamates
Enzymes
diphenyl
23 Citations (Scopus)
194 Downloads (Pure)

TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast cancer proliferation: a novel cancer-selective target pathway with therapeutic opportunities.

D'Costa, Z. C., Higgins, C., Ong, C. W., Irwin, G. W., Boyle, D., McArt, D. G., McCloskey, K., Buckley, N. E., Crawford, N. T., Thiagarajan, L., Murray, J. T., Kennedy, R. D., Mulligan, K. A., Harkin, D. P., Waugh, D. J. J., Scott, C. J., Salto-Tellez, M., Williams, R. & Mullan, P. B., 08 Feb 2014, In : Oncotarget. 5, 6, p. 1609-1620 12 p.

Research output: Contribution to journalArticle

Open Access
File
asparaginylendopeptidase
Cystatin M
Breast Neoplasms
Neoplasms
Cathepsins
2013
4 Citations (Scopus)

Expanded iron uta spectra - Probing the thermal stability limits in AGN clouds

Ferland, G. J., Kisielius, R., Keenan, F. P., Van Hoof, P. A. M., Jonauskas, V., Lykins, M. L., Porter, R. L. & Williams, R. J. R., 20 Apr 2013, In : Astrophysical Journal. 767, p. 1-12 123.

Research output: Contribution to journalArticle

active galactic nuclei
thermal stability
iron
inflection points
autoionization
2012
Metabotropic Glutamate 5 Receptor
Sulfonamides
Scaffolds
Glycine
Modulators
11 Citations (Scopus)
Metabotropic Glutamate 5 Receptor
Allosteric Site
Pulse amplitude modulation
Niacinamide
Amides
2011

Allosteric Modulators of Metabotropic Glutamate Receptor 5 for Treatment of Schizophrenia

Stauffer, S. R., Manka, J., Williams, R., Noetzel, M. J., Jadhav, S., Menion, U., Vinson, P., Niswender, C. M., Rook, J. M., Lindsley, C. W., Weaver, C. D., Conn, P. J., Blatt, T. N. & Days, E. L., 2011, In : CURRENT NEUROPHARMACOLOGY. 9, p. 11-12 2 p.

Research output: Contribution to journalArticle

34 Citations (Scopus)

Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

Williams, R., Manka, J. T., Rodriguez, A. L., Vinson, P. N., Niswender, C. M., Weaver, C. D., Jones, C. K., Conn, P. J., Lindsley, C. W. & Stauffer, S. R., 01 Mar 2011, In : Bioorganic & Medicinal Chemistry Letters. 21, 5, p. 1350-1353 4 p.

Research output: Contribution to journalArticle

Biphenyl Compounds
Lactams
Acetylene
Amphetamine
Scaffolds
2010
59 Citations (Scopus)

Context-Dependent Pharmacology Exhibited by Negative Allosteric Modulators of Metabotropic Glutamate Receptor 7

Niswender, C. M., Johnson, K., Miller, R., Ayala, J. E., Luo, H-K., Williams, R., Saleh, S., Orton, S., Weaver, C. D. & Conn, L., Mar 2010, In : Molecular Pharmacology. 77, 3, p. 459-468 10 p.

Research output: Contribution to journalArticle

Pharmacology
LY 341495
Calcium
Central Nervous System Diseases
Synaptic Transmission
118 Citations (Scopus)

Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable gamma-Secretase Inhibitor

Gillman, K. W., Starrett, J. E., Parker, M. F., Xie, K., Bronson, J. J., Marcin, L. R., McElhone, K. E., Bergstrom, C. P., Mate, R. A., Williams, R., Meredith, J. E., Burton, C. R., Barten, D. M., Toyn, J. H., Roberts, S. B., Lentz, K. A., Houston, J. G., Zaczek, R., Albright, C. F., Decicco, C. P. & 2 others, Macor, J. E. & Olson, R. E., 10 Jun 2010, In : ACS MEDICINAL CHEMISTRY LETTERS. 1, 3, p. 120-124 5 p.

Research output: Contribution to journalArticle

Amyloid Precursor Protein Secretases
Brain
Cerebrospinal fluid
Amyloid beta-Protein Precursor
Sulfonamides
143 Citations (Scopus)

Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity

Rodrigeuz, A. L., Grier, M. D., Jones, C. K., Herman, E. J., Kane, A. S., Smith, R. L., Williams, R., Zhou, Y., Days, E. L., Blatt, T. N., Jadhav, S., Menion, U., Vinson, P. N., Rook, J. M., Stauffer, S. R., Niswender, C. M., Lindsley, C. W., Weaver, C. D. & Conn, P. J., Dec 2010, In : Molecular Pharmacology. 78, 6, p. 1105-1123 19 p.

Research output: Contribution to journalArticle

Metabotropic Glutamate 5 Receptor
Anti-Anxiety Agents
Antipsychotic Agents
Rodentia
Anxiety
40 Citations (Scopus)

Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4

Williams, R., Zhou, Y., Niswender, C. M., Luo, Q., Conn, P. J., Lindsley, C. W. & Hopkins, C. R., 16 Jun 2010, In : ACS chemical neuroscience. 1, 6, p. 411-419 9 p.

Research output: Contribution to journalArticle

Scaffolds
Modulators
Structure-Activity Relationship
metabotropic glutamate receptor 4
20 Citations (Scopus)

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu(4) positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Engers, D. W., Gentry, P. R., Williams, R., Bolinger, J. D., Weaver, C. D., Menon, A., Conn, L., Lindsley, C. W., Niswender, C. M. & Hopkins, F., 01 Sep 2010, In : Bioorganic & Medicinal Chemistry Letters. 20, 17, p. 5175-5178 4 p.

Research output: Contribution to journalArticle

Modulators
Screening
Throughput
2009
81 Citations (Scopus)

A Novel Selective Muscarinic Acetylcholine Receptor Subtype 1 Antagonist Reduces Seizures without Impairing Hippocampus-Dependent Learning

Sheffler, D. J., Williams, R., Bridges, J., Xiang, J-J., Kane, A., Byun, N. E., Jadhav, S., Mock, M. M., Zheng, X., Lewis, C., Jones, C., Niswender, C. M., Weaver, C. D., Lindsley, C. W. & Conn, L., Aug 2009, In : Molecular Pharmacology. 76, 2, p. 356-368 13 p.

Research output: Contribution to journalArticle

Muscarinic Receptors
Hippocampus
Seizures
Learning
Central Nervous System Diseases
8 Citations (Scopus)

Discovery and Development of a Potent and Highly Selective Small Molecule Muscarinic Acetylcholine Receptor Subtype I (mAChR 1 or M-1) Antagonist In Vitro and In Vivo Probe

Weaver, C. D., Sheffler, D. J., Lewis, L. M., Bridges, T. M., Williams, R., Nalywajko, N. T., Kennedy, J. P., Mulder, M. M., Jadhav, S., Aldrich, L. A., Jones, C. K., Marlo, J., Niswender, C. M., Mock, M. M., Zheng, F., Conn, P. J. & Lindsley, C. W., 2009, In : Current Topics In Medicinal Chemistry. 9, 13, p. 1217-1226 10 p.

Research output: Contribution to journalArticle

Muscarinic Receptors
Area Under Curve
Microwaves
Ion Channels
Inhibitory Concentration 50
31 Citations (Scopus)

Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype.

Zhou, Y., Rodriguez, A. L., Williams, R., Weaver, C. D., Conn, P. J. & Lindsley, C. W., 15 Jun 2009, In : Bioorganic & Medicinal Chemistry Letters. 19(12), 12, p. 3209-3213 5 p.

Research output: Contribution to journalArticle

154 Citations (Scopus)

mGluR5 Positive Allosteric Modulators Facilitate both Hippocampal LTP and LTD and Enhance Spatial Learning

Ayala, J. E., Chen, Y., Banko, J. L., Sheffler, D. J., Williams, R., Telk, A. N., Watson, N., Xiang, Z., Zhang, Y., Jones, C. K., Lindsley, C. W., Olive, M. F. & Conn, P. J., Aug 2009, In : Neuropsychopharmacology. 34, 9, p. 2057-2071 15 p.

Research output: Contribution to journalArticle

Metabotropic Glutamate 5 Receptor
Long-Term Potentiation
Depression
Cognition
Hippocampus
40 Citations (Scopus)

Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead

Williams, R., Niswender, C. M., Luo, Q., Le, U., Conn, P. J. & Lindsley, C. W., 01 Feb 2009, In : Bioorganic & Medicinal Chemistry Letters. 19, 3, p. 962-966 5 p.

Research output: Contribution to journalArticle

Metabotropic Glutamate Receptors
Modulators
Pulse amplitude modulation
Lead
metabotropic glutamate receptor 4
37 Citations (Scopus)

Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273.

Engers, D. W., Rodriguez, A. L., Williams, R., Hammond, A. S., Venable, D., Oluwatola, O., Sulikowski, G. A., Conn, P. J. & Lindsley, C. W., 17 Apr 2009, In : ChemMedChem. 4, 4, p. 505-511 7 p.

Research output: Contribution to journalArticle

23 Citations (Scopus)

Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)

Williams, R., Johnson, K. A., Gentry, P. R., Niswender, C. M., Weaver, C. D., Conn, P. J., Lindsley, C. W. & Hopkins, C. R., 01 Sep 2009, In : Bioorganic & Medicinal Chemistry Letters. 19, 17, p. 4967-4970 4 p.

Research output: Contribution to journalArticle

Modulators
Parkinson Disease
Rodentia
metabotropic glutamate receptor 4
VU 0155041
16 Citations (Scopus)

Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS

Rodriguez, A. L., Zhou, Y., Williams, R., Weaver, C. D., Conn, P. J. & Lindsley, C. W., 01 Dec 2009, In : Bioorganic & Medicinal Chemistry Letters. 19, 23, p. 6502-6506 5 p.

Research output: Contribution to journalArticle

Modulators
Pharmacology
Pulse amplitude modulation
Scaffolds
Switches
2008

Allosteric modulators of metapotropic glutamate receptor subtype 5 as a novel approach for treatment of CNS disorders

Conn, P. J., Rodriguez, A. L., Ayala, J. E., Jones, C. K., Barrett, R., Niswender, C. M., Weaver, C. D., Jadhav, S., Sheffler, D. J., Hammond, A. S., Williams, R., Sharma, S. & Lindsley, C. W., Sep 2008, In : Neuropharmacology. 55, p. 593-593 1 p.

Research output: Contribution to journalArticle

123 Citations (Scopus)

An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission.

Shirey, J. K., Xiang, Z., Orton, D., Brady, A. E., Johnson, K. A., Williams, R., Ayala, J. E., Rodriguez, A. L., Wess, J., Weaver, C. D., Niswender, C. M. & Conn, P. J., Jan 2008, In : Nature Chemical Biology. 4, 1, p. 42-50 9 p.

Research output: Contribution to journalArticle

Synaptic Transmission
Acetylcholine
Allosteric Site
Pharmaceutical Chemistry
Central Nervous System Diseases
44 Citations (Scopus)

Design of potent GlyT1 inhibitors: In vitro and in vivo profiles

Bridges, J., Williams, R. & Lindsley, C. W., Dec 2008, In : Current opinion in molecular therapeutics. 10, 6, p. 591-601 11 p.

Research output: Contribution to journalArticle

Schizophrenia
Drug Industry
Prosencephalon
N-Methyl-D-Aspartate Receptors
Antipsychotic Agents

mGlur5 positive allosteric modulators facilitate both LTP and LTD induction in the rat hippocampal CA1 region

Ayalaa, J. E., Chen, Y., Banko, J. L., Sheffler, D. J., Williams, R. & Conn, P. J., Sep 2008, In : Neuropharmacology. 55, p. 586-586 1 p.

Research output: Contribution to journalArticle

Novel allosteric modulators of metabotropic glutamate receptors subtypes 2 and 5 for the treatment of schizophrenia

Jones, C. K., Xiang, F., Jones, A., Byun, N. E., Hackler, E. A., Rodriguez, A. L., Ayala, J. E., Niswender, C. M., Jadhav, S., Sheffler, D. J., Hammond, A. S., Barret, R., Thompson, A., Williams, R., Gore, E., Weaver, C. D., Lindsley, C. W. & Conn, P. J., Sep 2008, In : Neuropharmacology. 55, p. 603-603 1 p.

Research output: Contribution to journalArticle

14 Citations (Scopus)

Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists.

Bridges, T. M., Williams, R. & Lindsley, C. W., 01 Feb 2008, In : Bioorganic & Medicinal Chemistry Letters. 18(3), 3, p. 885-890 6 p.

Research output: Contribution to journalArticle

2006

Permissive antagonism induced by novel allosteric antagonists of metabotropic glutamate receptor 7

Niswender, C. M., Myers, K. A., Williams, R., Ayala, J. E., Luo, Q., Saleh, S., Jones, C. K., Orton, D., Weaver, C. D. & Conn, P. J., Dec 2006, In : Neuropsychopharmacology. 31, p. S127-S128 2 p.

Research output: Contribution to journalArticle

2002
207 Citations (Scopus)
Hydrogen bonds
Water
Acrylates
Catalysts
Aldehydes