COLLABORATIONS PHARMACEUTICALS INC — Department of Health and Human Services SBIR Phase II: NIGMS

Description

Project Summary We have recently used computational models to identify the protease inhibitor indinavirused as an antiviral for HIVas a positive allosteric modulator at thenicotinic acetylcholine receptorWe now propose to build on this discovery as well as other publications describing compounds that are positive allosteric modulators of thenicotinic acetylcholine receptorWe propose identifying further compounds that possess activity against this or one ofother targets implicated in Alzheimer s disease using a combination of Bayesian machine learning and in vitro assaysGenerating such data will enable us to potentially provide more specific compounds as well as building datasets that can be used to build predictive models to identify additional compounds with activity at these Alzheimer s targetsThese combined efforts should in the first instance provide commercially viable treatments which will be used to experimentally validate our computational models that can be shared with the Alzheimer s disease scientific communityWe are proposing to build and validate models based on public databasesselect compounds for testing and use the data generated as a starting point for further optimization Project Narrative Alzheimer s diseaseADis one of the most common neurodegenerative disorders that causes dementia and it is characterized by amyloid deposition of aAA peptideAprocessed from the amyloid precursor proteinAPPand neurofibrillary tanglesNFTMany palliative drugs are available for the disease but there is still an urgent need for curative drugs with greater efficacyWe need to understand the key factors involved in disease progression and their suitability as drug targets for discovering new drugs against Alzheimerandapos s diseaseWe hence propose to study several of these targets for Alzheimer s disease involving all the key steps in the pathwayincluding several old and new targetsWe will use ourAssay Centralsoftware to compile structure activity data for building computational modelsthat can be used to selected compounds to test activity in vitro as a starting point for further optimization