Histone lysine-specific demethylase 1 (LSD1, also known as KDM1A, BHC110, or AOF2), discovered in 2004, was the first reported functional protein that exhibited histone demethylase activity. LSD1 is a flavin adenine dinucleotide-dependent amino oxidase, which specifically removes mono- or dimethylated Lys4 of histone H3, or Lys9 of histone H3 to mediate changes in gene expression. Furthermore, LSD1 can also demethylate other nonhistone substrates such as the protein p53, DNA methyltransferase 1, the transcription factor E2F1, signal transducer, and activator of transcription 3, hypoxia-inducible factor, and myosin phosphatase target subunit 1. In recent years, LSD1 has been discovered to be overexpressed in various cancers, such as breast cancer, acute myeloid leukemia, gastric cancer, prostate cancer, hepatocellular carcinoma, and esophageal cancer, making it a promising therapeutic target for the treatment of cancer.
Downregulating the expression of LSD1 using siRNAs or small molecules was shown to inhibit cancer cell proliferation, invasion, migration, and differentiation and improve prognosis in various cancer cells and animal models. These findings emphasize the significance of exploiting potent LSD1 inhibitors for cancer therapy. To date, only seven LSD1 inhibitors (tranylcypromine, ORY-1001, ORY-2001, GSK-2879552, INCB059872, CC-90011, and IMG-7289) have been clinically assessed for cancer therapy, particularly for acute myeloid leukemia and small-cell lung cancer. Therefore, it is worth the effort to discover and develop the LSD1 inhibitors for cancer treatment. Except for the synthetic molecules, natural products have abundant scaffold diversity and structural complexity, which also have played a crucial role in the discovery of LSD1 inhibitors.
This Research Topic focuses on the research carried out on the design and synthesis of novel LSD1 inhibitors as well as their antitumor activities. Meanwhile, new research on natural LSD1 inhibitors is also encouraged.
This Research Topic encourages authors to submit Original Research and Review articles focused on but not limited to:
• Design and synthesis of novel LSD1 inhibitors involved with functional anticancer therapy.
• Targeted discovery and separation of new LSD1 inhibitors from natural plants.
• Functional and structural analysis research on natural LSD1 inhibitors derivatives.
• Synergism therapy with LSD1 inhibitors for improved cancer treatment.
• LSD1 inhibitors-based nano-drug delivery system for cancer therapy.
• Antitumor mechanism of LSD1 inhibitors in cancer cells.
• Clinical studies and their significance using LSD1 inhibitors in cancer treatment.
Histone lysine-specific demethylase 1 (LSD1, also known as KDM1A, BHC110, or AOF2), discovered in 2004, was the first reported functional protein that exhibited histone demethylase activity. LSD1 is a flavin adenine dinucleotide-dependent amino oxidase, which specifically removes mono- or dimethylated Lys4 of histone H3, or Lys9 of histone H3 to mediate changes in gene expression. Furthermore, LSD1 can also demethylate other nonhistone substrates such as the protein p53, DNA methyltransferase 1, the transcription factor E2F1, signal transducer, and activator of transcription 3, hypoxia-inducible factor, and myosin phosphatase target subunit 1. In recent years, LSD1 has been discovered to be overexpressed in various cancers, such as breast cancer, acute myeloid leukemia, gastric cancer, prostate cancer, hepatocellular carcinoma, and esophageal cancer, making it a promising therapeutic target for the treatment of cancer.
Downregulating the expression of LSD1 using siRNAs or small molecules was shown to inhibit cancer cell proliferation, invasion, migration, and differentiation and improve prognosis in various cancer cells and animal models. These findings emphasize the significance of exploiting potent LSD1 inhibitors for cancer therapy. To date, only seven LSD1 inhibitors (tranylcypromine, ORY-1001, ORY-2001, GSK-2879552, INCB059872, CC-90011, and IMG-7289) have been clinically assessed for cancer therapy, particularly for acute myeloid leukemia and small-cell lung cancer. Therefore, it is worth the effort to discover and develop the LSD1 inhibitors for cancer treatment. Except for the synthetic molecules, natural products have abundant scaffold diversity and structural complexity, which also have played a crucial role in the discovery of LSD1 inhibitors.
This Research Topic focuses on the research carried out on the design and synthesis of novel LSD1 inhibitors as well as their antitumor activities. Meanwhile, new research on natural LSD1 inhibitors is also encouraged.
This Research Topic encourages authors to submit Original Research and Review articles focused on but not limited to:
• Design and synthesis of novel LSD1 inhibitors involved with functional anticancer therapy.
• Targeted discovery and separation of new LSD1 inhibitors from natural plants.
• Functional and structural analysis research on natural LSD1 inhibitors derivatives.
• Synergism therapy with LSD1 inhibitors for improved cancer treatment.
• LSD1 inhibitors-based nano-drug delivery system for cancer therapy.
• Antitumor mechanism of LSD1 inhibitors in cancer cells.
• Clinical studies and their significance using LSD1 inhibitors in cancer treatment.