Design, Synthesis, and Structure-Activity Relationship of Novel LSD1 Inhibitors Based on Pyrimidine-Thiourea Hybrids as Potent, Orally Active Antitumor Agents

Ma L, et al., 58(4):1705-16., J Med Chem, 2015

The design and synthesis of small molecule inhibitors for histone lysine specific demethylase 1 (LSD1) is reported. One of the compounds from the novel inhibitor series based on pyrimidine-thiourea hybrids showed highest potency, selective inhibition of LSD1, and cytotoxicity against LSD1 overexpressed gastric cancer cells. A Pall ForteBio Octet RED96 equipped with SSA Biosensor probes was used to measure the interaction between small molecules and LSD1. Biotinylated LSD1 was captured onto SSA biosensors. These sensors subsequently blocked with biocytin. An unloaded set of sensors blocked with biocytin used for double referencing.

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