Michael Threadgill

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

Fingerprint Dive into the research topics where Michael Threadgill is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

2 Similar Profiles

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects

11 Finished

Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer

Threadgill, M. & Lloyd, M.

Worldwide Cancer Research

1/10/15 → 30/09/16

Project: UK charity

AMACR Targeted Drugs for Treating Advance Prostate Cancer

Lloyd, M., James, T., Jevglevskis, M., Nathubhai, A., Threadgill, M. & Woodman, T.

Prostate Cancer UK

1/02/15 → 30/07/18

Project: UK charity

Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer

Threadgill, M., Lloyd, M. & Nathubhai, A.

Worldwide Cancer Research

1/10/14 → 30/09/15

Project: UK charity

Refinement of a Polymeric System Delivering CGIs to Prostate Tumours

Threadgill, M., Lloyd, M. & Thompson, A.

Prostate Cancer UK

1/10/14 → 30/09/17

Project: UK charity

Advanced Inhibitors of Tankyrases 1 and 2, Critical Pathways in Cancer

Threadgill, M., Lloyd, M. & Nathubhai, A.

Worldwide Cancer Research

1/10/13 → 30/09/14

Project: UK charity

Research Output

81 Article
19 Poster
15 Other
5 Patent
7 More

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

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

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

Open Access

File

2 Citations (Scopus)

15 Downloads (Pure)

Novel 2-arylthiopropanoyl-CoA inhibitors of α-methylacyl-CoA racemase 1A (AMACR; P504S) as potential anti-prostate cancer agents

Jevglevskis, M., Nathubhai, A., Wadda, K., Lee, G. L., Al-Rawi, S., Jiao, T., Mitchell, P., James, T., Threadgill, M., Woodman, T. & Lloyd, M., 1 Nov 2019, In : Bioorganic Chemistry. 92, 103263.

Research output: Contribution to journal › Article

Open Access

File

66 Downloads (Pure)

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., 29 May 2019, (Accepted/In press) In : Molecular Biology.

Research output: Contribution to journal › Article