Dr Kamyar Afarinkia
|Position||Senior Lecturer in Medicinal Chemistry|
|Department||Institute of Cancer Therapeutics|
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Research Interests (key words only)
Drug Discovery and Medicinal Chemistry; Modulation of chemotactic signalling and its potential for cancer therapy; Inhibitors of glycosyl hydrolases (e.g. heparanase, golgi mannosidase II); Synthetic Organic Chemistry Diels-Alder cycloadditions of 2(H)-pyrones, 2(H)-pyridones and 2(H)-1,4-oxazin-2-ones; Asymmetric synthesis using chiral phosphorus; Total synthesis of biologically interesting and structurally unusual natural products; Peptide turn mimetics
Current PhD students
- Djev Ahmet (Oct 2012-June 2018)
- Mario Izidro (Jan 2015-Jan 2018)
- Rima Mroueh (Feb 2016- Feb 2019)
- Mohamed Anees (Feb 2016- Feb 2019)
- Shohreh Jafarinejad (joint with Dr William Martin) (Sept 2016-Sep 2022)
- Mashael Abdullah (Feb 2017-Feb 2021)
- Anwar Salem (Feb 2018-Feb 2021)
- Di Lu (joint with Dr Victoria Vinader) (Feb 2018 -2021)
PhD & Diploma of Imperial College (London), BSc (Hons) & Associateship of the Royal College of Science, London.
Antagonists of CCR7 in the treatment of dry eye disease
Clinical context and rationale
About 5% of all 50+ years olds suffer from the dry eye disease but the current treatment (artificial tear) is merely palliative. The disease is initiated and exacerbated through migration of lymphocytes into exocrine glands, under the control of the CCL19/CCL21/CCR7 axis.
We have identified ICT5888 as a novel chemokine receptor CCR7 antagonist. Optimisation of the potency of this lead compound has led to the identification of ICT13069, and ICT13124, two novel, potent and have shown that they prevent CCL19/ CCL21 induced chemotactic migration, invasion and immune response.
ICT13069 is being optimised for potency, water solubility and topical application (eye drop) in an animal model of the disease in an in vivo proof of concept. Subsequently, the plan is to initiate clinical progression of the compound.
Antagonists of CCR7 as novel agents for treatment of head & neck and pancreatic cancers
Clinical context and rationale
90% of cancer deaths are associated with metastasis, yet there are no clinical agents to prevent it. Our approach involves using a dual CXCR4/CCR7 antagonist to simultaneously prevent dissemination of cancer through vascular and lymphatic systems in cancers of the head & neck and pancreas.
Following on from our successful programme to identify novel CXCR4 antagonist ICT5122, and CCR7 antagonist ICT1313069 we are developing hybrid molecules with dual CXCR4 and CCR7 antagonism and have shown that it prevents chemotaxis, proliferation. Further preclinical investigation is on-going.
Glycomic tools for drug discovery
Objectives and rationale
Remodelling of the cell surface glycoproteins is associated with progression of disease. Our group has been at the forefront of developing methods for synthesis of glycomimetics using a Diels-Alder cycloaddition methodology.
We have published on methods for preparation of pseudo-disaccharides, control of stereochemistry at the pseudoanomeric position, and the first divergent synthesis of a pseudo-disaccharide library. We have used these tools to successfully investigate highly important targets such as heparanase and Golgi mannosidase II.
Targeting glioma cancer stem cells to combat disease resistance and recurrence
A joint project with Dr Victoria Vinader.
Course Leader: MSc Cancer Drug Discovery
Professional society memberships
- Associateship of the Royal College of Science (ARCS) (1987)
- Diploma of Imperial College (DIC) (1990)
- Fellow of the Royal Society of Chemistry (MRSC) (2016)
- Chartered Chemist (CChem) (1991)
- Member of American Chemical Society (1991)
- Member of the Bradford Institute for Health Research (2009)
- Member of the Specialist Group in Chemistry, University of London Higher Degrees Committee (2000-2006)
- SCI Young Chemist Panel Meeting Lecturer (Dec 2003-Jan 2004)
- Keynote Lecture at 16th International Conference on Organophosphorus Chemistry (2004)
- Over 15 invited speaking engagements nationally and internationally since 2010, most recently including:
- RSC Cancer Chemistry Inaugural Meeting (2001)
- 18th International Conference on Phosphorus Chemistry (ICPC 2010)
- Florida Heterocyclic and Synthetic Conference 2010 (Flohet-11)
- Peakdale Symposium Inaugural Lecture (2010)
- Author of seven book chapters, over 50 research papers and numerous conference presentations
- Invited Guest Editor for Special Issue on Chemokines in Future Medicinal Chemistry
- Over 900 citations in Science Citation Index
- Editorial Board of Arkivoc and Molecules. Reviewer for international journals as well as national (AICR, BBSRC, MRC and EPSRC, Breast Cancer Campaign, Leverhulme Trust) and international award granting bodies including Research Foundation Flanders (FWO) in Belgium; Health Research Board, Ireland; Agence Nationale de la Recherche (France); and Petroleum Research Fund (USA)
Publications are also listed in Bradford Scholars here
- Ahmed M.; Basheer, H.A.; Ayuso, J. M.; Ahmet, D.; Mazzini, M.; Patel, R.; Shnyder, S. D.; Vinader, V. Afarinkia, K. “Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines” Scientific Reports, 2017, 7, Article number: 1075.
- Haji Abdullahi, M.; Thompson, L. M.; Bearpark, M. J. Vinader, V. Afarinkia, K. “The role of substituents in retro Diels-Alder extrusion of CO2 from 2(H)-pyrone cycloadducts” Tetrahedron, 2016,72,6021-6024.
- Ayuso, J. M.; Basheer, H. A.; Monge, R.; Sánchez-Álvarez, P.; Doblaré, M.; Shnyder, S. D.; Vinader, V.; Afarinkia, K.; Fernández, L. J.; Ignacio Ochoa “Study of the chemotactic responses of multicellular spheroids in a microfluidic device” PLoS ONE, 2015, 10, e0139515.
- Vinader, V.; Sadiq, M.; Sutherland, M.; Huang, M.; Loadman, P. M.; Elsalem L.; Shnyder, S. D.; Cui, H.; Afarinkia,K.; Searcey, M.; Patterson, L. H.; Pors, K “Probing cytochrome P450-mediated activation with a truncated azinomycin analogue” Medicinal Chemistry Communications, 2015, 6, 187-191.
- Vinader, V.; Haji Abdullahi, M.; Patterson L.H.; Afarinkia, K. “Synthesis of a Pseudo-Disaccharide Library and its Application to the Characterisation of the Heparanase Catalytic Site” PLoS ONE, 2013,8, e82111.
- Vinader, V.; Ahmet, D.S.; Ahmed M.S.; Patterson L.H.; Afarinkia, K. “Discovery and Computer Aided Potency Optimization of a Novel Class of Small Molecule CXCR4 Antagonists” PLoS ONE, 2013, 8, e78744.
- Vinader, V.; Afarinkia, K. “Carbasugar Probes to Explore the Enzyme Binding Pocket at the Anomeric Position: Application to the Design of Golgi Mannosidase II Inhibitors” Current Medicinal Chemistry, 2013, 20, 3797-3801.
- Parry, L.J.; Vinader, V.; ScowenI. J., Patel, V. K.; Afarinkia, K. “Isolation and Characterisation of all Four Diastereomeric Intermediates from a Horner-Wittig Reaction” Phosphorus Sulfur and Silicon and the Related Elements, 2013, 188(1-3), 195-199.
- Vinader, V.; Afarinkia, K. “The Emerging Role of CXC Chemokines and Their Receptors in Cancer” Future Medicinal Chemistry, 2012, 7, 853-867.
- Vinader, V.; Afarinkia, K. “A Beginner’s Guide to Chemokines” Future Medicinal Chemistry, 2012, 7, 845-852.
- Vinader, V.; Al-Saraireh, Y.; Wiggins, H. L.; Rappoport, J. Z.; Shnyder, S. D.; Patterson L. H.; Afarinkia, K. “An Agarose Spot Chemotaxis Assay for Chemokine Receptor Antagonists”, Journal of Pharmacological and Toxicological Methods, 2011, 64, 213-216.
- Afarinkia, K.; Royappa, M.; ScowenI. J. “Synthesis and Folding Properties of α-Hydroxy and α-Amino Phenylphosphinate Pseudopeptides” Phosphorus Sulfur and Silicon and the Related Elements, 2011, 186(4), 809-813.
- Afarinkia, K.;Royappa, M.; Scowen,I. J.; Steed, J. W.; Yu, H-w. “A synthesis of oligomeric α-hydroxy phenylphosphinates and a study of the conformational preferences of the dimers” Organic and Biological Chemistry, 2010, 600-606.
- Afarinkia, K.;Haji Abdullahi, M.; ScowenI. J. “A Synthesis of Carbasugar-Sugar Pseudodisaccharides via a Cycloaddition-Cycloreversion Reaction of 2(H)-Pyran-2-ones” Organic Letters, 2010, 12, 5564-5566.
- Afarinkia, K.; Haji Abdullahi, M.; ScowenI. J. “A New, General Method for the Synthesis of Carbasugar-Sugar Pseudodisacchrides” Organic Letters, 2009, 11, 5182-5184.
- Afarinkia, K.; Ndibwami, A. “A general synthesis of phenantridinone alkaloids” Synlett, 2007,1940-1944.
- Afarinkia, K.; Bahar A.; Neuss, J. “Synthesis of hydrophobically modified analogues of adenophorine” Synlett, 2007, 1375-1378.