Michael Threadgill

Prof

Accepting PhD Students

20002019
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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

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

Projects 2005 2018

Research Output 2000 2019

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., 7 Sep 2019, In : Bioorganic Chemistry. 92, 103264.

Research output: Contribution to journalArticle

1 Citation (Scopus)
2 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., 21 Jan 2019, In : Organic & Biomolecular Chemistry. 17, 5, p. 1266-1276 11 p.

Research output: Contribution to journalArticle

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., 7 Sep 2019, In : Bioorganic Chemistry. 92, 103263.

Research output: Contribution to journalArticle

Open Access
File

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 journalArticle

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., 1 Sep 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

Thesis

Approaches to new DNA-repair inhibitors for applications in cancer therapy

Author: Dhami, A., 1 Dec 2008

Supervisor: Threadgill, M. (Supervisor) & Lloyd, M. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

Collected publications, 1982-1997

Author: Threadgill, M. D., 1998

Student thesis: Doctoral ThesisDoctor of Science (DSc)

File

Design and synthesis of selective inhibitors of poly(ADP-ribose)polymerase-2

Author: Sunderland, P., 1 Jan 2010

Supervisor: Threadgill, M. (Supervisor), Thompson, A. (Supervisor) & Martin, N. G. (External person) (Supervisor)

Student thesis: Doctoral ThesisPhD

File

Development of Prodrugs to Deliver Super-Potent Drugs to Prostate Tumors

Author: Twum, E., 5 Nov 2013

Supervisor: Threadgill, M. (Supervisor), Thompson, A. (Supervisor) & Lloyd, M. (Supervisor)

Student thesis: Doctoral ThesisPhD

File

Development of Selective Inhibitors of Dihydrofolate Reductase (DHFR) of Mycobacterium Tuberculosis

Author: Alfaraj, R., 31 Dec 2013

Supervisor: Threadgill, M. (Supervisor), Lloyd, M. (Supervisor) & Thompson, A. (Supervisor)

Student thesis: Doctoral ThesisMPhil

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