Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor

Bioorganic & Medicinal Chemistry Letters
2019.0

Abstract

Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.

Knowledge Graph

Similar Paper

Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor
Bioorganic & Medicinal Chemistry Letters 2019.0
Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors
Bioorganic & Medicinal Chemistry Letters 2021.0
Design and synthesis of tranylcypromine derivatives as novel LSD1/HDACs dual inhibitors for cancer treatment
European Journal of Medicinal Chemistry 2017.0
Design and synthesis of benzylpiperidine inhibitors targeting the menin–MLL1 interface
Bioorganic & Medicinal Chemistry Letters 2016.0
Phenothiazine-Based LSD1 Inhibitor Promotes T-Cell Killing Response of Gastric Cancer Cells
Journal of Medicinal Chemistry 2023.0
Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors
European Journal of Medicinal Chemistry 2017.0
Design, synthesis and in vitro evaluation of stilbene derivatives as novel LSD1 inhibitors for AML therapy
Bioorganic & Medicinal Chemistry 2018.0
Synthesis and evaluation of small molecule inhibitors of LSD1 for use against MYCN-expressing neuroblastoma
European Journal of Medicinal Chemistry 2022.0
Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: A novel class of irreversible inhibitors of histone demethylase KDM1A
European Journal of Medicinal Chemistry 2014.0
Progress towards small molecule menin-mixed lineage leukemia (MLL) interaction inhibitors with in vivo utility
Bioorganic & Medicinal Chemistry Letters 2015.0