title: Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors.
abstract: In 2001, two years before the disclosure of the CERT-associated Cer transfer machinery, N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamides (HPAs) were described as the first, and to date unique, family of intracellular Cer trafficking inhibitors. The dodecanamide derivative, HPA-12, turned out to be a benchmark as a cellular inhibitor of CERT-mediated de novo sphingomyelin biosynthesis. In only 15 years after its first disclosure, this compound has prompted a growing number of biological and chemical studies. Its initial chemical development closely paralleled the study of the CERT protein. It was only after its structural revision in 2011 that HPA-12 received broad attention from the synthetic chemistry community, leading to novel analogues with enhanced protein binding. This Minireview aims at presenting an exhaustive report of the syntheses of HPA-12 and analogues. Biological activities of this CERT inhibitor and structure-activity relationships are also presented to afford a comprehensive overview of the chemistry and biology of the HPA series.
authors.affiliation: Department of Organic Chemistry, Slovak University of Technology, Radlinského 9, 81237, Bratislava, Slovak Republic.
authors.forename: Dušan
authors.initials: D
authors.lastname: Berkeš
authors.affiliation: Normandie Univ, UNIHAVRE, CNRS, URCOM, Université du Havre, URCOM EA-3221, INC3 M CNRS FR-3038, UFR des Sciences et Techniques, 25 rue Philippe Lebon, B.P. 1123, 76063, Le Havre Cedex, France.
authors.forename: Adam
authors.initials: A
authors.lastname: Daïch
authors.affiliation: SPCMIB, UMR5068 CNRS-, Université Paul Sabatier-Toulouse III, 118 route de Narbonne, 31062, Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Santos
authors.affiliation: SPCMIB, UMR5068 CNRS-, Université Paul Sabatier-Toulouse III, 118 route de Narbonne, 31062, Toulouse, France.
authors.forename: Stéphanie
authors.identifier: http://orcid.org/0000-0002-7250-6188
authors.initials: S
authors.lastname: Ballereau
authors.affiliation: SPCMIB, UMR5068 CNRS-, Université Paul Sabatier-Toulouse III, 118 route de Narbonne, 31062, Toulouse, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Génisson
mesh_terms: D000577:Amides / Q000737:chemistry*; D002465:Cell Movement; D002518:Ceramides / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002518:Ceramides; C441643:N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
keywords: 1,3-amino alcohol; CERT protein; HPA-12; ceramide; sphingolipids