Discovery of natural product-like spirooxindole derivatives as highly potent and selective LSD1/KDM1A inhibitors for AML treatment

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…It also exhibited promising in vivo results in mice and is regarded as promising for acute myeloid leukemia (AML) disease. 11 Further, a review appeared spanning the therapeutic potentials of spirooxindoles as antiviral agents. 12 Based on the above discussion, it is apparent that the development and adoption of three-dimensional spirocycles as pharmacophores has paved the way for new chemical entities employed in drug discovery.…”

“…It also exhibited promising in vivo results in mice and is regarded as promising for acute myeloid leukemia (AML) disease. 11 Further, a review appeared spanning the therapeutic potentials of spirooxindoles as antiviral agents. 12…”

Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A

“…Abnormal expression of LSD1 in various cancers promotes cancer progression and is closely related to the survival and prognosis of patients ( Figure 3 ) ( Ramírez-Ramírez et al, 2020 ; Zhang et al, 2020 ). Given that LSD1 is a potential therapeutic target for cancer, many targeted inhibitors of LSD1 with excellent anticancer activity have been reported, and some of these inhibitors have entered clinical trials ( Maes et al, 2018 ; Wimalasena et al, 2020 ; Fang et al, 2021 ; Yang et al, 2022 ).…”

Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential

“…Other LSD1 inhibitors such as SP2509 [ 122 ], NCD38 [ 123 ], JL1037 [ 124 ] were at the preclinical stage. What’s more, FY-56, a promising LSD1 inhibitor, weakened the proliferation ability of leukemia cells, induced the accumulation of H3K4me1/2 and the activation of p53, and reduced HOXA9 and MEIS1 mRNA levels, exhibiting a therapeutic potential in AML [ 125 ]. Another two LSD1 inhibitors Higenamine [ 126 ], tranylcypromine derivatives MS142 also showed to inhibit LSD1 activity [ 127 ], while further investigation on the role of these LSD inhibitors in solid tumors is required.…”