Dr Kamyar Afarinkia
Associate Professor
Faculty/Dept/School |
School of Pharmacy and Medical Sciences (Faculty of Life Sciences) |
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k.afarinkia@bradford.ac.uk | |
Telephone | +441274 235831 |
Biography
Kamyar Afarinkia graduated with 1st class honours BSc degree in Chemistry from Imperial College and obtained his PhD in Organic Chemistry under the supervision of Prof Charles Rees, FRS & Prof Sir John Cadogan. His PhD dissertation was funded by an Overseas Research Scholarship and an extramural studentship from BP and resulted in the first synthesis of 1,2-azaphosphetidine (analogues of ß-lactam in which the C=O bond is replaced by a P=O bond). He then took up a two year Postdoctoral Fellowship at the Johns Hopkins University, Baltimore, working with Prof Gary Posner on the synthesis of analogues of calcitriol (vitamin D3). After his postdoc, he joined Glaxo as a Senior Chemist working on projects ranging from diabetes to hypertension. He left pharma to become a lecturer and then senior lecturer in medicinal and synthetic organic chemistry at King’s College London, and moved to the University of Bradford to join the newly established Institute of Cancer Therapeutics (ICT).
Research
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. Key achievements 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. Clinical progression 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. Key achievements 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. Key achievements 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.Publications
Peer Reviewed Journal | |
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Title | A new route to tricyclane sesquiterpenoids: total synthesis of α-ekasantalic acid. (2019) |
Authors | Lomba L;Afarinkia K;Vinader V; |
Journal | Organic and Biomolecular Chemistry |
DOI | 10.1039/c9ob00630c |
Title | Control of the stereochemistry of C14 hydroxyl during the total synthesis of withanolide E and physachenolide C (2018) |
Authors | Anees, Muhammad; Nayak, Sanjit; Afarinkia, Kamyar; Vinader, Victoria |
Title | Hypoxia modulates CCR7 expression in head and neck cancers (2018) |
Authors | Basheer, Haneen A.; Pakanavicius, E.; Cooper, Patricia A.; Shnyder, Steven D.; Martin, L.; Hunter, K.D.; Vinader, Victoria; Afarinkia, Kamyar |
Title | Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines (2017) |
Authors | Ahmed, Mohaned S.A.; Basheer, Haneen A.; Ayuso, J.M.; Ahmet, Djevdet; Mazzini, Marco; Patel, Roshan; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar |
Title | The role of substituents in retro Diels-Alder extrusion of CO2 from 2(H)-pyrone cycloadducts (2016) |
Authors | Abdullahi, Mohamed H.; Thompson, L.M.; Bearpark, M.J.; Vinader, Victoria; Afarinkia, Kamyar |
Title | The role of substituents in retro Diels–Alder extrusion of CO |
Authors | Abdullahi M.;Thompson L.;Bearpark M.;Vinader V.;Afarinkia K. |
Journal | Tetrahedron |
DOI | 10.1016/j.tet.2016.07.066 |
Title | Probing cytochrome P450-mediated activation with a truncated azinomycin analogue (2015) |
Authors | Vinader, Victoria; Sadiq, Maria; Sutherland, Mark H.; Huang, M.Y.; Loadman, Paul M.; Elsalem, Lina M.I.; Shnyder, Steven D.; Cui, H.J.; Afarinkia, Kamyar; Searcey, M.; Patterson, Laurence H.; Pors, Klaus |
Journal | MedChemComm |
DOI | dx.doi.org/10.1039/c4md00411f |
Title | Study of the chemotactic response of multicellular spheroids in a microfluidic device (2015) |
Authors | Ayuso, J.M.; Basheer, Haneen A.; Monge, R.; Sánchez-Álvarez, P.; Doblare, M.; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar; Fernandez, L.J.; Ochoa, I. |
Title | Carbasugar probes to explore the enzyme binding pocket at the anomeric position: Application to the design of Golgi mannosidase II inhibitors (2013) |
Authors | Vinader M.;Afarinkia K. |
Journal | Current Medicinal Chemistry |
DOI | 10.2174/09298673113209990180 |
Title | Synthesis of a pseudo-disaccharide library and its application to the characterisation of the heparanase catalytic site (2013) |
Authors | Vinader V.;Haji-Abdullahi M.;Patterson L.;Afarinkia K. |
Journal | PLoS ONE |
DOI | 10.1371/journal.pone.0082111 |
Title | Discovery and computer aided potency optimization of a novel class of small molecule CXCR4 antagonists. (2013) |
Authors | Vinader V.;Ahmet D.;Ahmed M.;Patterson L.;Afarinkia K. |
Journal | PLoS ONE |
DOI | 10.1371/journal.pone.0078744 |
Title | An agarose spot chemotaxis assay for chemokine receptor antagonists (2011) |
Authors | Vinader V.;Al-Saraireh Y.;Wiggins H.;Rappoport J.;Shnyder S.;Patterson L.;Afarinkia K. |
Journal | Journal of Pharmacological and Toxicological Methods |
DOI | 10.1016/j.vascn.2011.01.004 |
Title | A synthesis of carbasugar-sugar pseudodisaccharides via a cycloaddition-cycloreversion reaction of 2 H -Pyran-2-ones (2010) |
Authors | Afarinkia K.;Abdullahi M.;Scowen I. |
Journal | Organic Letters |
DOI | 10.1021/ol102358s |
Title | A synthesis of oligomeric α-hydroxy phenylphosphinates and a study of the conformational preferences of the dimers (2010) |
Authors | Afarinkia K.;Royappa M.;Scowen I.;Steed J.;Yu H. |
Journal | Organic and Biomolecular Chemistry |
DOI | 10.1039/b917737j |
Title | A new, general method for the synthesis of carbasugar-sugar pseudodisaccharides (2009) |
Authors | Afarinkia K.;Abdullahi M.;Scowen L. |
Journal | Organic Letters |
DOI | 10.1021/ol901960y |
Title | Synthesis of hydrophobically modified analogues of adenophorine (2007) |
Authors | Afarinkia K.;Bahar A.;Neuss J. |
Journal | Synlett |
DOI | 10.1055/s-2007-980359 |
Title | A general synthesis of phenanthridinone alkaloids (2007) |
Authors | Afarinkia K.;Ndibwami A. |
Journal | Synlett |
DOI | 10.1055/s-2007-984540 |
Title | When Z′ = 2 is better than Z′ = 1 - supramolecular centrosymmetric hydrogen-bonded dimers in chiral systems (2006) |
Authors | Anderson K.;Afarinkia K.;Yu H.;Goeta A.;Steed J. |
Journal | Crystal Growth and Design |
DOI | 10.1021/cg0603265 |
Title | An Investigation of the Diels-Alder Cycloadditions of 2(H)-1,4-Oxazin-2-ones. (2005) |
Authors | Afarinkia, Kamyar; Bahar, A.; Bearpark, M.J.; Garcia-Ramos, J.; Ruggiero, A.; Neuse, J.; Vyas, M. |
Title | Investigation of the Diels-Alder cycloadditions of 2(H)-1,4-oxazin-2-ones. (2005) |
Authors | Afarinkia K;Bahar A;Bearpark MJ;Garcia-Ramos Y;Ruggiero A;Neuss J;Vyas M; |
Journal | Journal of Organic Chemistry |
DOI | 10.1021/jo051646i |
Title | An experimental and computational investigation of the Diels-Alder cycloadditions of halogen-substituted 2(H)-pyran-2-ones. (2005) |
Authors | Afarinkia K;Bearpark MJ;Ndibwami A; |
Journal | Journal of Organic Chemistry |
DOI | 10.1021/jo048213k |
Title | Preparation of asymmetric alpha-ketophosphonates by [3,3]-sigmatropic shift of enolphosphonates. (2004) |
Authors | Afarinkia, Kamyar; Twist, A; Yu, H-w. |
Title | Control of electron demand in the cycloadditions of 2(H)-1,4-oxazin-2-ones (2004) |
Authors | Afarinkia K.;Bahar A.;Neuss J.;Vyas M. |
Journal | Tetrahedron Letters |
DOI | 10.1016/j.tetlet.2004.07.105 |
Title | 2(H)-1,4-Oxazin-2-ones as ambident azadienes (2004) |
Authors | Afarinkia K.;Bahar A.;Neuss J.;Ruggiero A. |
Journal | Tetrahedron Letters |
DOI | 10.1016/j.tetlet.2004.03.183 |
Title | Hewitt reaction revisited (2003) |
Authors | Afarinkia K.;Yu H. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(02)02647-3 |
Title | A Computational and Experimental Investigation of the Diels-Alder Cycloadditions of Halogen Substituted 2(H)-pyran-2-one (2003) |
Authors | Afarinkia, Kamyar; Bearpark, M.J.; Ndibwami, A. |
Title | Computational and experimental investigation of the Diels-Alder cycloadditions of 4-chloro-2(H)-pyran-2-one. (2003) |
Authors | Afarinkia K;Bearpark MJ;Ndibwami A; |
Journal | Journal of Organic Chemistry |
DOI | 10.1021/jo0348827 |
Title | Conformational preferences in 2-alkyl, 2-alkanoyl and 2-aroyl-2-oxo-1,3,2-oxazaphosphorinanes (2001) |
Authors | Afarinkia K.;Angell R.;Jones C.;Lowman J. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(00)02050-5 |
Title | Asymmetric nucleophilic addition to vinylphosphonates (part I) (2000) |
Authors | Afarinkia, K; Binch, HM; De Pascale, E |
Journal | Synlett |
Title | Asymmetric nucleophilic addition to vinylphosphonates (part II) (2000) |
Authors | Afarinkia, K; Binch, HM; Forristal, I |
Journal | Synlett |
Title | Diels-Alder cycloaddition of 5-aryl-2-pyrones (2000) |
Authors | Afarinkia K.;Berna-Canovas J. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(00)00744-9 |
Title | The anionic route to tricyclanes (2000) |
Authors | Afarinkia K.;Mahmood F. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(99)02270-4 |
Title | A novel and concise synthesis of (±) 2-epi-Validamine (1999) |
Authors | Afarinkia K.;Mahmood F. |
Journal | Tetrahedron |
DOI | 10.1016/S0040-4020(99)00071-X |
Title | Acceleration of nucleophilic addition to vinylphosphonates and vinyl phosphine oxides by chlorotrimethylsilane (1998) |
Authors | Afarinkia K.;Binch H.;Modi C. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(98)01612-8 |
Title | A novel synthesis of (±) 2-epi-validamine (1998) |
Authors | Afarinkia K.;Mahmood F. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(98)01610-4 |
Title | Highly efficient Diels-Alder cycloadditions of 2-pyridones with bulky N-sulfonyl substituent (1998) |
Authors | Afarinkia K.;Mahmood F. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(97)10585-8 |
Title | A mild and stereoselective synthesis of β-phosphonylacrylates (1998) |
Authors | Afarinkia K.;Evans M.;Graham J.;Jimenez-Bueno G. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(97)10540-8 |
Title | Facile enolisation of α-ketophosphonates (1997) |
Authors | Afarinkia K.;Echenique J.;Nyburg S. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(97)00157-3 |
Title | Unusual stereoselectivity in Diels-Alder cycloaddition of 5-bromopyrone (1997) |
Authors | Afarinkia K.;Daly N.;Gomez-Farnos S.;Joshi S. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(97)00352-3 |
Title | A reinvestigation of the structure of the erythro and xanthoapocyanine dyes: Some unusual aspects of quinoline chemistry (1996) |
Authors | Afarinkia K.;Ansari M.;Bird C.;Gyambibi I. |
Journal | Tetrahedron Letters |
DOI | 10.1016/0040-4039(96)00940-9 |
Title | Asymmetric Total Synthesis, X-ray Crystallography, and Preliminary Biological Evaluation of 1-(1′-Hydroxyethyl)-25-hydroxyvitamin D |
Authors | Posner G.;Dai H.;Afarinkia K.;Murthy N.;Guyton K.;Kensler T. |
Journal | Journal of Organic Chemistry |
DOI | 10.1021/jo00077a052 |
Title | Synthesis of 1,2-azaphosphetidines (1992) |
Authors | Afarinkia K.;Cadogan J.;Rees C. |
Journal | Journal of the Chemical Society - Series Chemical Communications |
DOI | 10.1039/C39920000285 |
Title | Four-membered heterocycles containing one phosphorus and one other heteroatom (1992) |
Authors | Afarinkia K. |
Journal | Heterocycles |
DOI | 10.3987/REV-91-437 |
Title | DIASTEREOSELECTIVITY IN THE FORMATION OF PHOSPHORUS CARBON BONDS (1992) |
Authors | AFARINKIA, K; CADOGAN, JIG; REES, CW |
Journal | Synlett |
Title | Diels-Alder Cycloadditions Using Nucleophilic 2-Pyridones. Regiocontrolled and Stereocontrolled Synthesis of Unsaturated, Bridged, Bicyclic Lactams (1992) |
Authors | Posner G.;Vinader V.;Afarinkia K. |
Journal | Journal of Organic Chemistry |
DOI | 10.1021/jo00041a010 |
Title | Diels-Alder cycloadditions of 2-pyrones and 2-pyridones (1992) |
Authors | Afarinkia K.;Vinader V.;Nelson T.;Posner G. |
Journal | Tetrahedron |
DOI | 10.1016/S0040-4020(01)85607-6 |
Title | 5-Bromo-2-pyrone: An easily prepared ambiphilic diene and a synthetic equivalent of 2-pyrone in mild, thermal, Diels-Alder cycloadditions (1992) |
Authors | Afarinkia K.;Posner G. |
Journal | Tetrahedron Letters |
DOI | 10.1016/S0040-4039(00)74757-5 |
Title | ADDITION OF SILYL PHOSPHITES TO ALPHA,BETA-UNSATURATED IMINES (1992) |
Authors | AFARINKIA, K; CADOGAN, JIG; REES, CW |
Journal | Synlett |
Title | 3-BROMO-2-PYRONE - AN EASILY PREPARED CHAMELEON DIENE AND A SYNTHETIC EQUIVALENT OF 2-PYRONE IN THERMAL DIELS-ALDER CYCLOADDITIONS (1991) |
Authors | POSNER, GH; NELSON, TD; KINTER, CM; AFARINKIA, K |
Journal | TETRAHEDRON LETT |
Title | SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS VIA SILYL ESTERS OF PHOSPHORUS-ACIDS (1990) |
Authors | AFARINKIA, K; REES, CW; CADOGAN, JIG |
Journal | Tetrahedron |
DOI | 10.1016/S0040-4020(01)87899-6 |
Title | SYNTHESIS OF PHOSPHINIC AND PHOSPHONIC ANALOGS AND C-ARYLGLYCINES (1990) |
Authors | AFARINKIA, K; CADOGAN, JIG; REES, CW |
Journal | Synlett |