spark great interests in seeking po

spark great interests in seeking potential combination therapeutics usefulness for tumor treatment with anti-PD-1 immunotherapy. Like intervention on histones deacetylation (HDAC), intervention/modifications on histones methylation such as LSD1 are expected to generatetherapeuticdrugsinthenearfuture.15,16 TherearemanyLSD1inhibitorsreportedinliterature.17–22 Among them,thefollowingthreesmallmolecules,allbelongingtoirreversible tranylcypromine derivatives, were advanced into the clinical stage: ORY-1001 (1),23 GSK-2879552 (2),24,25 and CC-90011 (3) (Fig. 1).26 Thesethreeinhibitorsarecurrentlybeingevaluatedinhumansaloneor incombination with other therapeutic agents. Despitethe great interestsanddeepenedknowledgeofLSD1fieldfromrecentyears,5,27there isnoLSD1inhibitorapprovedasdruguptodate.Continuousseeking for new inhibitors targeting LSD1 is undoubtedly necessary and important. Benzofuran moiety is one of the important structural units widely foundinnaturalproductsandsyntheticcompoundsindrugdiscovery. Compounds bearing benzofuran moiety generally possess certain biological activities such as anti-proliferation activity through multiple mechanisms.28–31 Forinstance,Moracinrelatedcompoundsarebioactive benzofuran derivatives isolated from species of the moraceae family.MoracinO(4)wasreportedfortheirabilitytoinhibitHIF-1activation, with IC50 value of 0.14 μM.31,32BNC-105P (5), a tubulin