Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

Vivreon Biosciences is pleased to apply for NIA SBIR SolicitationPAVivreon Biosciences is an innovative life sciences company that is developing a series of novel small moleculeCachannel inhibitors for the treatment of Alzheimer s diseaseADOur lead compound series achieves neuroprotection by an entirely new mechanisminhibition of Carelease activated CaCRACchannels to block microgliosisVivreon seeks NIA funding to bridge the gap between discovery and developmentWe will optimize our promising lead compound series through medicinal chemistryUpon successful completion of the programour preclinical candidate will be the first to specifically target the CRAC pathway for neuroprotection in ADthus comprising an entirely new tool in the battle against ADVivreon has discovered a lead compound series with oral bioavailability that penetrates into the central nervous systemCNSvery efficientlyshows no neurotoxicity in the Irwin test of CNS integrityand demonstrates neuroprotection in a mouse model of microgliosisexperimental autoimmune encephalitisThe lead series inhibits microgliosis by blocking CRAC channel activity with nM potencysuppressing MNFB activitywhile preserving MphagocytosisWe will improve on these favorable properties through medicinal chemistry lead optimization followed by biological screeningOur lead presents several routes for modification that could lead to improved drug like propertiesand these routes will be pursued to identify a preclinical candidate molecule suitable for future Investigational New DrugINDenabling studiesThe candidate will be identified using an animal model suitable for ADXFADDrBlurtonJonesUniversity of CaliforniaIrvineThe final aim for this proposal is synthesis and characterization of the first CRAC channel inhibitor for AD therapy