Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators
Tangallapally R, Subramanian C, Yun M, Edwards A, Sharma L, Yang L, Creed K, Wang J, Jackowski S, Rock C, White S, Lee R. Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators. Journal Of Medicinal Chemistry 2024, 67: 14432-14442. PMID: 39136313, PMCID: PMC11345825, DOI: 10.1021/acs.jmedchem.4c01211.Peer-Reviewed Original ResearchConceptsCoA levelsAcyl-CoA levelsIncreased CoA levelsBiosynthesis pathwayPantothenate kinaseStructure-guided designCoA biosynthesisPropionic acidemiaCoenzyme APantothenate kinase-associated neurodegenerationSmall molecule activationCultured cellsBiosynthesisMolecule activationStructure-activity relationshipEnzymeActivation potentialPharmacokinetic profilePhosphopantothenateClinical testingPanKCoAKinaseMetabolic stabilityIsoforms
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