Kamyar Afarinkia

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.