Projects per year
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
Award Date: 1 Jan 1998
Doctor of Philosophy, University of Cambridge
Award Date: 1 Jan 1981
Master of Arts, University of Cambridge
Award Date: 1 Jan 1978
Education, Durham University
Award Date: 30 Jun 1975
Bachelor of Arts, University of Cambridge
Award Date: 1 Jan 1974
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Network
Projects
- 11 Finished
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Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer
1/10/15 → 30/09/16
Project: UK charity
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AMACR Targeted Drugs for Treating Advance Prostate Cancer
Lloyd, M., James, T., Jevglevskis, M., Nathubhai, A., Threadgill, M. & Woodman, T.
1/02/15 → 30/07/18
Project: UK charity
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Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer
Threadgill, M., Lloyd, M. & Nathubhai, A.
1/10/14 → 30/09/15
Project: UK charity
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Refinement of a Polymeric System Delivering CGIs to Prostate Tumours
Threadgill, M., Lloyd, M. & Thompson, A.
1/10/14 → 30/09/17
Project: UK charity
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Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer
Threadgill, M., Lloyd, M. & Nathubhai, A.
1/10/13 → 30/09/14
Project: UK charity
Research Output
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Derivatives of a PARP inhibitor TIQ-A through synthesis of 8-alkoxythieno[2,3-c]isoquinolin-5(4H)-ones
Maksimainen, M., Nurmesjärvi, A., Terho, R., Threadgill, M., Lehtiö, L. & Heiskanen, J., 2020, In: ACS OMEGA.Research output: Contribution to journal › Article › peer-review
Open AccessFile -
PARP10 influences the proliferation of colorectal carcinoma cells, a preliminary study
Wu, C., Xiao, M., Wang, Y., Threadgill, M., Li, M., Tang, Y., Lin, X., Yang, L., Li, Q. & Li, X., 31 Mar 2020, In: Molecular Biology. 54, 2, p. 220-228 9 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile15 Downloads (Pure) -
Stimulation of insulin secretion by 5-methylcoumarins and its sulfur analogues isolated from Clutia lanceolata Forssk
Ahmed, S., Nur-e-Alam, M., Parveen, I., Coles, S. J., Hafizur, R. M., Hameed, A., Orton, J. B., Threadgill, M. D., Yousaf, M., Alqahtani, A. M. & Al-Rehaily, A. J., 1 Feb 2020, In: Phytochemistry. 170, 112213.Research output: Contribution to journal › Article › peer-review
Open AccessFile1 Citation (Scopus)2 Downloads (Pure) -
Identification of novel small-molecule inhibitors of α-methylacyl-CoA racemase (AMACR; P504S) and structure-activity relationships
Petrova, Y., Wadda, K., Nathubhai, A., Jevglevskis, M., Mitchell, P., James, T., Threadgill, M., Woodman, T. & Lloyd, M., 1 Nov 2019, In: Bioorganic Chemistry. 92, 103264.Research output: Contribution to journal › Article › peer-review
Open AccessFile4 Citations (Scopus)17 Downloads (Pure) -
New flavonoids from the Saudi Arabian plant: Retama raetam which stimulates secretion of insulin and inhibits α-glucosidase
Nur-e-Alam, M., Yousaf, M., Parveen, I., Hafizur, R., Ghani, U., Ahmed, S., Hameed, A., Threadgill, M. & Al-Rehaily, A. N., 7 Feb 2019, In: Organic & Biomolecular Chemistry. 17, 5, p. 1266-1276 11 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile4 Citations (Scopus)39 Downloads (Pure)
Thesis
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Collected publications, 1982-1997
Author: Threadgill, M. D., 1998Student thesis: Doctoral Thesis › Doctor of Science (DSc)
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