Scott Webster
Personal Chair of Medicines Discovery
Address
- Street
-
The Queen's Medical Research Institute
Edinburgh BioQuarter
47 Little France Crescent - City
- Edinburgh
- Post code
- EH16 4TJ
Research summary
The primary focus of my research is drug discovery. I conduct translational research with a focus on discovering and developing small molecules as drugs for the treatment of conditions such as Alzheimer’s disease, acute pancreatitis, liver fibrosis and multiple sclerosis. This is research is highly collaborative with close involvement of both academic and industrial collaborators across a range of discplines. My research has led to the discovery of a number of potent small molecule inhibitors of target enzymes, with the most advanced compound, UE2343 (XanamemTM), out-licensed and progressing through clinical trials in humans. My group provides expertise in target validation through assay devlopment and in vitro screening to lead optimisation and clinical candidate selection.
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Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice
(10 pages)
In:
Nature Communications, vol. 12
DOI: https://doi.org/10.1038/s41467-021-21273-6
Research output: Contribution to Journal › Article (Published) -
Vitamin A deficiency impairs contextual fear memory in rats: abnormalities in glucocorticoid pathway
In:
Journal of Neuroendocrinology
DOI: https://doi.org/10.1111/jne.12802
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Kynurenine 3-monooxygenase is a critical regulator of renal ischemia–reperfusion injury
In:
Experimental and Molecular Medicine, vol. 51
DOI: https://doi.org/10.1038/s12276-019-0210-x
Research output: Contribution to Journal › Article (E-pub ahead of print) -
11Beta‐hydroxysteroid dehydrogenase‐1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis
(15 pages)
In:
Hepatology, vol. 67, pp. 2167-2181
DOI: https://doi.org/10.1002/hep.29734
Research output: Contribution to Journal › Article (Published) -
Diclofenac identified as a kynurenine 3-monooxygenase binder and inhibitor by molecular similarity techniques
In:
ACS Omega
DOI: https://doi.org/10.1021/acsomega.7b02091
Research output: Contribution to Journal › Article (Published) -
Exploring N-acyl-4-azatetracyclo[5.3.2.0.0]dodec-11-enes as 11β-HSD1 Inhibitors
In:
Molecules, vol. 23
DOI: https://doi.org/10.3390/molecules23030536
Research output: Contribution to Journal › Article (Published) -
Quantification of 11β-hydroxysteroid dehydrogenase 1 kinetics and pharmacodynamic effects of inhibitors in brain using mass spectrometry imaging and stable-isotope tracers in mice
In:
Biochemical Pharmacology, vol. 148, pp. 88-99
DOI: https://doi.org/10.1016/j.bcp.2017.12.013
Research output: Contribution to Journal › Article (Published) -
Detecting Drug-Target Binding in Cells using Fluorescence Activated Cell Sorting Coupled with Mass Spectrometry Analysis
In:
Methods and Applications in Fluorescence
DOI: https://doi.org/10.1088/2050-6120/aa8c60
Research output: Contribution to Journal › Article (Published) -
In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis
In:
Scientific Reports, vol. 7, pp. 10806
DOI: https://doi.org/10.1038/s41598-017-10521-9
Research output: Contribution to Journal › Article (Published) -
Design, synthesis and in vivo study of novel pyrrolidine-based 11β-HSD1 inhibitors for age-related cognitive dysfunction
(17 pages)
In:
European Journal of Medicinal Chemistry, vol. 139, pp. 412-428
DOI: https://doi.org/10.1016/j.ejmech.2017.08.003
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase
(12 pages)
In:
Nature Communications, vol. 8
DOI: https://doi.org/10.1038/ncomms15827
Research output: Contribution to Journal › Article (Published) -
The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis
In:
Bioorganic & Medicinal Chemistry Letters, vol. 27
DOI: https://doi.org/10.1016/j.bmcl.2017.02.078
Research output: Contribution to Journal › Article (Published) -
Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis
In:
Journal of Medicinal Chemistry
DOI: https://doi.org/10.1021/acs.jmedchem.7b00055
Research output: Contribution to Journal › Article (Published) -
Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™)
In:
British Journal of Pharmacology
DOI: https://doi.org/10.1111/bph.13699
Research output: Contribution to Journal › Article (Published) -
Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness
(9 pages)
In:
Nature Medicine, vol. 22, pp. 771-779
DOI: https://doi.org/10.1038/nm.4115
Research output: Contribution to Journal › Article (Published) -
Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines that Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase
In:
Journal of Medicinal Chemistry
DOI: https://doi.org/10.1021/acs.jmedchem.6b00065
Research output: Contribution to Journal › Article (Published) -
11β-Hydroxysteroid Dehydrogenase type 1 is expressed in neutrophils and restrains an inflammatory response in male mice
(9 pages)
In:
Endocrinology, vol. 157, pp. 2928-2936
DOI: https://doi.org/10.1210/en.2016-1118
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional non-linear feedback
In:
Cell Death and Disease, vol. 7, pp. e2197
DOI: https://doi.org/10.1038/cddis.2016.87
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis
(8 pages)
In:
Nature Medicine, vol. 22, pp. 202-209
DOI: https://doi.org/10.1038/nm.4020
Research output: Contribution to Journal › Article (Published) -
Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis
In:
Scientific Reports, vol. 6, pp. 33951
DOI: https://doi.org/10.1038/srep33951
Research output: Contribution to Journal › Article (Published)