lsd 1

Lsd1-in-20 is a potent dual inhibitor of LSD1/G9a with Ki values of 0.44 and 0.68 μM, respectively. LSD1-IN-20 showed antiproliferative activity against THP-1 leukemia cells and MDA-MB-231 breast cancer cells in vitro, with IC50 of 0.51 and 1.60 μM, respectively, at 72 h.

LSD1-IN-30 is a lysine-specific demethylase 1 (LSD1) inhibitor with anticancer activity for the study of small cell lung cancer and acute myeloid leukemia.

LSD1-IN-5 increases dimethylated Lys4 of histone H3, shows no effect on expression of LSD1. LSD1-IN-5 is a potent and reversible inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 121 nM.

LSD1-IN-6 increases dimethylated Lys4 of histone H3, shows no effect on expression of LSD1. LSD1-IN-6 is a potent and reversible inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 123 nM.

GSK-LSD1 dihydrochloride (GSK-LSD1 2HCl) is a specificity irreversible LSD1 inhibitor (IC50: 16 nM). The selectivity of GSK-LSD1 for LSD1 is >1000 fold over other closely related FAD utilizing enzymes (i.e. MAO-A, LSD2, MAO-B).

Pulrodemstat benzenesulfonate (CC-90011 benzenesulfonate) is a potent and orally active inhibitor of lysine specific demethylase-1 (LSD1) with anticancer activity.

LSD1-IN-27 is a potent LSD1 inhibitor with an IC50 value of 13 nM.LSD1-IN-27 inhibited the stemness and migration of gastric cancer cells.LSD1-IN-27 inhibited the expression of PD-L1 in BGC-823 and MFC cells.LSD1-IN-27 potentiated the T-cell immune response against gastric cancer.

GSK-LSD1 is a selective LSD1 inhibitor with potential anticancer activity that attenuates the expression of CTGF/CCN2, MMP13, LOXL4, and waveform proteins in cancer cells.GSK-LSD1 regulates the cell cycle, induces apoptosis, and can be used to study breast cancer.

LSD1/HDAC6-IN-1 is an orally active dual inhibitor targeting lysine specific demethylase 1 (LSD1) and histone deacetylase 6 (HDAC6), demonstrating promising anti-tumor activity, particularly valuable for multiple myeloma (MM) research [1].

LSD1-IN-35 (Compound Z-1) is a selective inhibitor of LSD1, exhibiting an IC50 of 108 nM. This compound inhibits the demethylation of H3K4me1/2 and acts as an immunomodulator. Additionally, LSD1-IN-35 enhances the responsiveness of gastric cancer cells to T-cell killing by reducing PD-L1 expression, thereby weakening the PD-1/PD-L1 interaction.

LSD1/HDAC-IN-1 (compound 2) serves as an effective inhibitor of both HDAC and LSD1, demonstrating IC50 values of 0.125 nM, 0.373 nM, 0.0118 nM, 0.103 nM, and 0.571 μM for HDAC1, HDAC2, HDAC6, HDAC8, and LSD1 respectively. This compound plays a crucial role in cancer research.

LSD1-IN-37 (Compound 5g) is an inhibitor of lysine-specific demethylase 1 (LSD1), developed through an efficient synthesis strategy incorporating a hexafluoroisopropyl group. This approach does not require metal catalysts and offers excellent reaction stability and adaptability. LSD1-IN-37 exhibits outstanding LSD1 inhibitory activity and has potential for further research.

LSD1/HDAC-IN-2 (Compound 20c) acts as an inhibitor targeting both LSD1 and several HDACs, specifically HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with IC50 values of 39.0, 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively. This compound effectively inhibits the proliferation of cancer cells, notably colorectal cancer cells. LSD1/HDAC-IN-2 induces cell cycle arrest at the G2/M phase, inhibits cell migration, and triggers apoptosis in HCT-116 and HT-29 cells. Additionally, it demonstrates antitumor activity in mouse models without causing significant toxicity at a dose of 20 mg/kg.

LSD1-IN-38 (Compound 23e) is a reversible, orally active inhibitor of lysine-specific demethylase 1 (LSD1), with an IC50 of 1.2 nM. It effectively inhibits the proliferation of cancer cells MV4-11, Kasumi-1, and NCI-H526 with IC50 values of 5, 4, and 11 nM, respectively. Furthermore, LSD1-IN-38 activates CD86 expression with an EC50 of 0.034 μM and induces differentiation in MV4-11 cells. In mouse models, this compound demonstrates antitumor activity.

LSD1/EGFR-IN-1 (compound L-1) is an effective inhibitor of LSD1, EGFRT790M/L858R, and EGFRL858R/T790M/C797S, with IC50 values of 6.24, 2.06, and 5.01 μM, respectively. This compound plays a significant role in cancer research.

LSD1-IN-39 (Compound 14) is a reversible inhibitor of LSD1 with an IC50 of 0.18 μM, showing broad-spectrum antiproliferative activity against cancer cells, inhibiting HepG2 cell migration, and suppressing epithelial-mesenchymal transition. Additionally, LSD1-IN-39 exhibits antitumor activity in mouse models.

LSD1-IN-42 (Compound 7ae) is an orally active LSD1 inhibitor that significantly suppresses LSD1 activity (IC50 = 0.08 μM). It reduces PD-L1 expression and enhances the tumor-killing effect of T cells. LSD1-IN-42 demonstrates notable anti-gastric cancer activity by inhibiting tumor cell invasion and migration.

LSD1-IN-40 (Compound 9e) is a potent LSD1 inhibitor with an IC50 value of 9.85 nM. It exhibits greater selectivity for LSD1 over MAO and hERG. LSD1-IN-40 shows significant inhibitory activity against leukemia cells (MV-4-11, HL-60, and THP-1 cells) and can induce apoptosis in MV-4-11 cells. This compound holds potential for research in acute myeloid leukemia.

LSD1-IN-32 (compound 11e) is a potent inhibitor of LSD1, with an IC50 value of 0.99 µM. It effectively impedes RANKL-induced osteoclastogenesis, bone resorption, and F-actin ring formation, indicating its potential use in osteoporosis research.

Tubulin/LSD1-IN-1 is a potent dual inhibitor of tubulin polymerization and LSD1 (IC50 = 1.72 μM), exhibiting broad-spectrum antiproliferative activity against cancer cell lines. By targeting the colchicine binding site, it disrupts the microtubule network in gastric cancer cells. Tubulin/LSD1-IN-1 enhances methylation levels of H3K4me1/2 and H3K9me2/3, facilitating epigenetic regulation. It induces G2/M phase arrest, promotes apoptosis, and effectively inhibits colony formation in gastric cancer cells.

LSD1-IN-43 is a highly selective, reversible, and orally active LSD1 inhibitor with blood-brain barrier permeability, showing an IC50 value of 0.8 μM. It exhibits lower inhibitory activity against LSD1 homologs MAO-A and MAO-B. LSD1-IN-43 significantly inhibits Aβ aggregation and enhances neuronal cell viability induced by Aβ. It is applicable in Alzheimer's disease (AD) research.

LSD1-IN-44 (Compound 19) is an LSD1 inhibitor with an IC50 of 0.02 μM for the LSD1-CoREST enzyme complex. It exhibits significant antischistosomal activity against newly transformed schistosomula (NTS) and adult Schistosoma mansoni, though its effect on larvae shows some delay. LSD1-IN-44 demonstrates no notable toxicity to human cells and is applicable for schistosomiasis research.

LSD1/2-IN-3 is a selective inhibitor of lysine-specific demethylase 1 (LSD1) with a Ki value of 11 nM, compared to 7 μM for LSD2. Aberrant expression of LSD1 is found in tumor stem cells, and LSD1/2-IN-1 inhibits LSD1 cell proliferation [1].

LSD1/2-IN-4, a derivative of PCPA, functions as an inhibitor for both lysine-specific demethylase 1 (LSD1) and lysine-specific demethylase 2 (LSD2), demonstrating K i values of 0.11 μM and 130 μM against LSD1 and LSD2, respectively. This compound is utilized in researching various cancers, notably T-cell acute lymphoblastic leukemia (TALL) [1].