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Michael Threadgill

Prof

  • 5 WEST 3.9

Accepting PhD Students

20002018
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Personal profile

Research interests

The research focus of the Threadgill group is drug design and delivery. We work on the application of medicinal chemistry (structure-based drug design, chemical synthesis, biochemical and cell biological evaluation) to developing new cancer treatments. Where the biochemistry of other diseases is similar (haemorrhagic shock, stroke, myocardial infarction, etc.), our work has branched out into these areas. We also research new synthetic methods in organic heterocyclic chemistry. Collaborations in Bath, Aberystwyth, Finland, India and Poland are important to our work.

Current research

PARP inhibitors

The poly(ADP-ribose)polymerases (PARPs) are a family of enzymes which use ADP-ribose units from NAD+ to build poly(ADP-ribose) polymers on target proteins. PARP-1 regulates DNA repair and gene expression through NF-κB. We developed 5-AIQ as a leading inhibitor of PARP-1, potent in models of metastatic cancer, inflammation and ischaemia-reperfusion injury. We have designed some of the most isoform-selective inhibitors of PARP-2 reported to date. Currently, we use structure-based drug design to develop new potent inhibitors of the tankyrases (PARP-5a,5b) in a major project funded by AICR.

Tumour-selective delivery of drugs

In cancer chemotherapy, it is important that the cytotoxic drug acts selectively in the tumour and we have been actively researching selective delivery of cytotoxic drugs for several years. Funded by the Prostate Cancer Charity, we are constructing polymeric prodrugs which release their load of extreme cytotoxins selectively in prostate tumours, through retention by the EPR effect and cleavage by the protease PSA.

Tuberculosis

Building on previous experience in inhibition of dihydrofolate reductase in cancer, we are using structure-based drug design to develop selective inhibitors of this enzyme in Mycobacterium tuberculosis.

Natural products

Collaborating with Aberystwyth University, we identify and profile natural product cinnamates from cultivated grasses, for industrial applications.

Earlier projects

Inhibitors of NOS, sirtuins, Pin1; isotopic synthesis; gene delivery; sulfoximine chemistry; biochemical kinetic isotope effects.

Education/Academic qualification

Doctor of Science, University of Bath

Doctor of Philosophy, University of Cambridge

Master of Arts, University of Cambridge

Education, Durham University

Bachelor of Arts, University of Cambridge

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  • 4 Similar Profiles
Tankyrases Chemical Compounds
Poly(ADP-ribose) Polymerases Medicine & Life Sciences
Acyl Coenzyme A Chemical Compounds
Esters Chemical Compounds
Coenzyme A Medicine & Life Sciences
Phenols Chemical Compounds
Acids Chemical Compounds
Enzymes Medicine & Life Sciences

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Projects 2005 2018

Research Output 2000 2018

Structure-activity relationships of rationally designed AMACR 1A inhibitors

Jevglevskis, M., Lee, G. L., Nathubhai, A., Petrova, Y., James, T., Threadgill, M., Woodman, T. & Lloyd, M. 30 Apr 2018 In : Bioorganic and Medicinal Chemistry. 79, p. 145-154 10 p.

Research output: Contribution to journalArticle

Acyl Coenzyme A
Enzyme activity
Coenzyme A
Assays
Esters

Synthesis and solid-state conformations of 6S,8aR/S-6-alkyl-3,3-dimethyltetrahydrooxazolo[3,4-a]pyrazine-5,8-diones (pseudoproline DKPs).

Beauchard, A., Dufton, H. F., Odumah, K., Jaggers, R. H., Mahon, M. F., Wood, P. J. & Threadgill, M. 2018 In : Indian Journal of Heterocyclic Chemistry.

Research output: Contribution to journalArticle

Diketopiperazines
Pyrazines
S 6
Conformations
Dipeptides

A convenient colorimetric assay for α-methylacyl-CoA racemase (AMACR; P504S) and testing of inhibitors

Jevglevskis, M., Lee, G. L., Nathubhai, A., James, T., Threadgill, M., Woodman, T. & Lloyd, M. 21 Apr 2017 (Unpublished)

Research output: Contribution to conferenceAbstract

File
Coenzyme A
Inhibitory Concentration 50
Acyl Coenzyme A
Prostatic Neoplasms
S 10
2 Citations

A novel colorimetric assay for α-methylacyl-CoA racemase 1A (AMACR; P504S) utilizing the elimination of 2,4-dinitrophenolate

Jevglevskis, M., Lee, G. L., Nathubhai, A., Petrova, Y., James, T., Threadgill, M., Woodman, T. & Lloyd, M. 7 May 2017 In : Chemical Communications. 53, 37, p. 5087-5090 4 p.

Research output: Contribution to journalArticle

Open Access
Assays
Ibuprofen
Fatty acids
Fatty Acids
Degradation
9 Citations

Highly potent and isoform-selective dual-site-binding tankyrase/Wnt signaling inhibitors that increase cellular glucose uptake and have anti-proliferative activity

Nathubhai, A., Haikarainen, T., Koivunen, J., Murthy, S., Koumanov, F., Lloyd, M., Holman, G., Pihlajaniemi, T., Tosh, D., Lehtio, L. & Threadgill, M. 26 Jan 2017 In : Journal of Medicinal Chemistry. 60, 2, p. 814-820

Research output: Contribution to journalArticle

Open Access
File
Tankyrases
Inhibitory Concentration 50
Protein Isoforms
Binding Sites
Glucose