lsd1

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-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-24 is a selective and potent LSD1 inhibitor with an IC50 value of 0.247 μM.LSD1-IN-24 induces PD-L1 expression and enhances the T cell killing response, and can be used in cancer-related diseases.

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.

Tranylcypromine (2-PCPA) hydrochloride (SKF-385 HCl), a Monoamine Oxidase inhibitor, is effective in the treatment of major depression, dysthymic disorder, and atypical depression.

Vafidemstat (ORY-2001) is a selective, orally active lysyl-histone demethylase (LSD1) MAO-B inhibitor that crosses the blood-brain barrier for the study of neurological diseases.

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).

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.

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.

HSP90 LSD1-IN-1 (compound 6) is a dual inhibitor of HSP90 and LSD1. This compound effectively inhibits the proliferation of prostate cancer cell lines PC-3 and DU145, with GI50 values of 0.24 μM and 0.30 μM, respectively.

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-36, an effective LSD1 inhibitor with an IC50 value of 0.8 nM, induces cell apoptosis and arrests the cell cycle. This compound also exhibits antitumor activity.

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 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 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].

LSD1-IN-22 is a potent inhibitor of Lysine-specific demethylase 1 (LSD1) with a K_i value of 98 nM, exhibiting anti-proliferative activity against certain cancer cells [1].

LSD1-IN-12 (compound 2) is an effective inhibitor of LSD1, with inhibitory Ki values of 1.1 μM (LSD1), 61 μM (LSD2), 2.3 μM (MAO-A), and 3.5 μM (MAO-B) [1].

LSD1-IN-15 (compound 1b) is a potent LSD1 inhibitor that inhibits LSD1-CoREST, MAO-A, and MAO-B with IC50 values of 0.149, 0.028, and 0.327 μM, respectively. LSD1-IN-15 induces cell growth arrest in LNCaP cells of prostate cancer, with an IC50 value of 9.9 μM [1].