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Published TCIMAIL newest issue No.197
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Inhibitors of Lysine-specific Demethylases (LSDs)
LSD (lysine specific demethylase) is an enzyme which uses FAD (flavin adenine dinucleotide) as a coenzyme to demethylate methylated lysine in histone proteins. LSD has two isoforms (LSD1, LSD2). LSD1 is expected to be a therapeutic target for cancer, while LSD2 has numerous unknown functions and is currently under research to elucidate its function.1-3) LSD Inhibitor S1024 (1) and LSD Inhibitor S1025 (2) exhibit equally potent inhibitory activity against LSD1 and different inhibitory activity against LSD2. 1 is also known to increase intracellular histone-modified H3K4me2 through its inhibitory effect.4) In addition, 1 and 2 can be used for the research to elucidate the function of LSD2 taking advantage of the gap of their activity.
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References
- 1) LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target
- 2) Overexpression of the shortest isoform of histone demethylase LSD1 primes hematopoietic stem cells for malignant transformation.
- 3) Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases
- 4) Structure–Activity Relationship and In Silico Evaluation of cis- and trans-PCPA-Derived Inhibitors of LSD1 and LSD2
