Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies.

Basic Information

ID: ALA3421542

Journal: ACS Med Chem Lett

Title: Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies.

Authors: Valente S, Rodriguez V, Mercurio C, Vianello P, Saponara B, Cirilli R, Ciossani G, Labella D, Marrocco B, Ruoppolo G, Botrugno OA, Dessanti P, Minucci S, Mattevi A, Varasi M, Mai A.

Abstract: The pure four diastereomers (11a-d) of trans-benzyl (1-((4-(2-aminocyclopropyl)phenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate hydrochloride 11, previously described by us as LSD1 inhibitor, were obtained by enantiospecific synthesis/chiral HPLC separation method. Tested in LSD1 and MAO assays, 11b (S,1S,2R) and 11d (R,1S,2R) were the most potent isomers against LSD1 and were less active against MAO-A and practically inactive against MAO-B. In cells, all the four diastereomers induced Gfi-1b and ITGAM gene expression in NB4 cells, accordingly with their LSD1 inhibition, and 11b and 11d inhibited the colony forming potential in murine promyelocytic blasts.

CiteXplore: 25699146

DOI: 10.1021/ml500424z

Patent ID: ┄