Abstract：
Aberrant expression of the epigenetic regulator lysine-specific demethylase 1 (LSD1) has been associated with the incidence of many diseases, particularly cancer, and it has evolved as a promising epigenetic target over the years for treatment. The advent of LSD1 inhibitor-based clinical utility began with tranylcypromine, and it is now considered an inevitable scaffold in the search for other irreversible novel LSD1 inhibitors (IMG-7289 or bomedemstat, ORY1001 or iadademstat, ORY-2001 or vafidemstat, GSK2879552, and INCB059872). Moreover, numerous reversible inhibitors for LSD1 have been reported in the literature, including clinical candidates CC-90011 (pulrodemstat) and SP-2577 (seclidemstat). There is parallel mining for peptide-based LSD1 inhibitors, which exploits the opportunities in the LSD1 substrate binding pocket. This Review highlights the research progress on reversible and irreversible peptide/peptide-derived LSD1 inhibitors. For the first time, we comprehensively organized the peptide-based LSD1 inhibitors from the design strategy. Peptide inhibitors of LSD1 are classified as H3 peptide and SNAIL1 peptide derivatives, along with miscellaneous peptides that include naturally occurring LSD1 inhibitors.
摘要：
表观遗传调节因子赖氨酸特异性脱甲基酶1（LSD1）的异常表达与许多疾病的发生有关。特别是癌症，多年来，它已经发展成为一种有希望的表观遗传靶标。基于LSD1抑制剂的临床应用的出现始于tranylcypromine，现在，在寻找其他不可逆的新型LSD1抑制剂（IMG-7289或bomedemstat，ORY1001或iadadademstat,ORY-2001或vafidemstat，GSK2879552和INCB059872）。此外，文献中已经报道了许多LSD1的可逆抑制剂，包括临床候选人CC-90011（pulrodemstat）和SP-2577（seclidemstat）。有平行挖掘基于肽的LSD1抑制剂，它利用了LSD1底物结合口袋中的机会。本文综述了可逆和不可逆肽/肽衍生LSD1抑制剂的研究进展。第一次,我们从设计策略中全面组织了基于肽的LSD1抑制剂。LSD1的肽抑制剂分为H3肽和SNAIL1肽衍生物，以及包括天然存在的LSD1抑制剂的各种肽。
