Executive Summary : | The research aims to identify potential lead molecules for the optimization of clinical candidates for various diseases, including Alzheimer's disease, cancer, and inflammatory diseases. The project will focus on identifying two sets of lead molecules: one with brain penetration for neurodegenerative diseases like Alzheimer's disease and ageing, and the other non-brain penetrant compounds for inflammatory and oncogenic diseases. The main hypothesis will be to evaluate if two sets of lead molecules can be identified in one project: one with brain penetration for neurodegenerative diseases like Alzheimer's disease and ageing, and the other non-brain penetrant compounds for inflammatory and oncogenic diseases. The project is challenging but highly feasible due to preclinical validation. Experiments will include designing and synthesizing novel compounds with strong intellectual property, identifying key interactions for potency and selectivity, and conducting in-vitro and in-vivo experiments to identify potent and selective compounds with reasonable pharmacokinetic and pharmacodynamic properties. The significance of this research lies in its potential to identify RIP1 kinase inhibitors, with a priority on identifying novel, potent, and selective compounds for neurodegenerative indications like Alzheimer's disease and ageing. Alzheimer's disease is the most common form of dementia and is the only condition that cannot be cured, prevented, or slowed down. Non-brain penetrant compounds can also provide potential leads for the treatment of oncogenic diseases and inflammatory disorders like inflammatory bowel disease and psoriasis. |