Histone Demethylase Inhibitor

EED-IN-4 is an orally active, EZH2-selective immunomodulator and EED-H3K27me3 inhibitor (EED, IC₅₀=28.21 nM) with anti-inflammatory activity. In mouse models, EED-IN-4 preferentially and persistently accumulates in lymph nodes after oral administration. By reducing the H3K27me3 level of dendritic cells and inhibiting their migration, EED-IN-4 reduces the infiltration of immune cells into the central nervous system and effectively alleviates spinal cord inflammation. EED-IN-4 shows weak inhibitory activity against hERG channels and is non-mutagenic, with no obvious toxicity observed upon long-term oral administration. EED-IN-4 can be used for the research of multiple sclerosis.

LSD1-IN-39 (Compound 14) is a reversible inhibitor for LSD1 with an IC₅₀ of 0.18 μM. LSD1-IN-39 exhibits broad-spectrum anti-proliferative activity against cancer cells, inhibits the cell migration of HepG2 and inhibits the epithelial-mesenchymal transition. LSD1-IN-39 exhibits antitumor activity in mouse models.

KDM5B-IN-3 (Compound 5) is a histone lysine specific demethylase 5B (KDM5B/JARID1B) inhibitor with an IC₅₀ of 9.32 μM. KDM5B-IN-3 can be used for the research of gastric cancer.

LSD1-IN-19 (compound 29) is a potent, non-covalent and selective LSD1 inhibitor, with K_i of 0.108 μM and K_D of 0.068 μM, respectively. LSD1-IN-19 shows antiproliferative activity in THP-1 leukemia cells and MDA-MB-231 breast cancer cells, with IC₅₀ (72 h) of 0.17 and 0.40 μM, respectively.

HDAC-IN-57 is an orally active inhibitor of histone deacetylases (HDAC), with IC₅₀s of 2.07 nM, 4.71 nM, 2.4 nM and 107 nM for HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-57 can inhibits LSD1, with IC₅₀ of 1.34 μΜ. HDAC-IN-57 induces apoptosis, and has anti-tumor activity.

LSD1-IN-42 (Compound 7ae) is an orally active LSD1 inhibitor that potently inhibits LSD1 activity (IC₅₀ = 0.08 μM). LSD1-IN-42 downregulates PD-L1 expression and enhances T cell-mediated tumor killing effects. LSD1-IN-42 demonstrates significant anti-gastric cancer activity by inhibiting tumor cell invasion and migration.

CBN209350 is a selective KDM4 inhibitor with an IC₅₀ of 4 μM. CBN209350 exerts antiproliferative effects on prostate cancer cells. CBN209350 can be used for the research of prostate cancer.

(S,S)-TAK-418 is a potent inhibitor of lysine-specific demethylase 1 (LSD1), demonstrating significant normalization of aberrant gene expression in neurodevelopmental disorders. (S,S)-TAK-418 also ameliorates ASD-like behaviors in rodent models affected by maternal exposure to valproate or poly I:C. (S,S)-TAK-418 modulates gene expression differently across various models and ages, indicating its potential as a therapeutic agent for conditions like autism spectrum disorder and schizophrenia.

Zavondemstat (QC8222; TACH 101) sodium is an orally active pan-KDM4 inhibitor, with a IC₅₀ ≤ 0.08 μM against human KDM4A-D and a Kᵢ of 0.52 μM against human KDM4C. Zavondemstat sodium induces cell apoptosis, causes S-phase cell cycle arrest, reduces the population of tumor-initiating cells and inhibits cancer cell proliferation. Zavondemstat sodium suppresses tumor growth and induces tumor regression in mouse xenograft models. Zavondemstat sodium can be used for the research of various cancers including colorectal cancer, esophageal squamous cell carcinoma and triple-negative breast cancer.

LSD1-IN-12 (compound 2) is a potent LSD1 inhibitor, with K_i values of 1.1 μM (LSD1), 61 μM (LSD2), 2.3 μM (MAO-A), and 3.5 μM (MAO-B), respectively.

LSD1-IN-14 is a potent and selective LSD1 inhibitor (IC₅₀=0.89 μM). LSD1-IN-14 can significantly inhibit the proliferation of A549 and THP-1 cells and induce the apoptosis of tumor cells.

LSD1-IN-13 (compound 7e) is an orally active and potent LSD1 inhibitor, with an IC₅₀ of 24.43 nM. LSD1-IN-13 can activate CD86 expression, with an EC₅₀ of 470 nM. LSD1-IN-13 induces differentiation of AML (acute myeloid leukemia) cell lines.

LSD1-IN-20 (compound 1) is a potent dual non-covalent LSD1/G9a inhibitor, with K_i values of 0.44 and 0.68 μM, respectively. LSD1-IN-20 shows antiproliferative activity in THP-1 leukemia cells and MDA-MB-231 breast cancer cells, with IC₅₀ (72 h) of 0.51 and 1.60 μM, respectively.

FY-56 is a highly potent and selective LSD1/KDM1A inhibitor (IC₅₀=42 nM) and exhibits high selectivity over MAO-A/B. FY-56 induces differentiation of MOLM-13 and MV4-11 cell and has the potential for AML research.

LSD1-IN-10 is a LSD1/MAO inhibitor with LSD1 IC₅₀ of 5 nM, MAO-A IC₅₀ of 16 μM, and MAO-B IC₅₀ of 7.4 μM. LSD1-IN-10 suppresses enzymatic activity of LSD1, MAO-A, and MAO-B. LSD1-IN-10 can be used for the research of cancer, alzheimer's disease, parkinson's disease, huntington's disease.

LSD1-IN-40 (Compound 9e) is a potent LSD1 inhibitor, with an IC₅₀ of 9.85 nM. LSD1-IN-40 exhibits exceptional selectivity for LSD1 over both MAOs and hERG. LSD1-IN-40 exhibits significant inhibitory activity against leukemia cells (MV-4-11, HL-60, and THP-1 cells). LSD1-IN-40 can induce apoptosis in MV-4-11 cells. LSD1-IN-40 has the potential for the research of acute myeloid leukemia.

LSD1/2-IN-3 is a selective inhibitor of lysine-specific demethylase 1 (LSD1), with a K_i value of 11 nM instead of 7 μM for LSD2. There is aberrant expression of LSD1 in cancer stem cells, LSD1/2-IN-1 inhibits LSD1 cell proliferation.

KDM2B-IN-3 is a histone demethylase KDM2B inhibitor extracted from patent WO2016112284A1, compound 183c. KDM2B-IN-3 can be used for the research of cancer.

TPC-144 is a LSD1/KDM1A inhibitor. TPC-144 inhibits LSD1, and leads to a decrease in the protein level of DNMT1, causing low methylation of the LINE-1 element. TPC-144 can also produce a synergistic effect with Decitabine (HY-A0004) (a DNMT inhibitor), jointly promoting DNA demethylation and thereby inducing differentiation and apoptosis of leukemia cells. TPC-144 has also demonstrated anti-tumor efficacy in acute myeloid leukemia (AML) models. TPC-144 can be used for the study of AML.

LSD1-IN-49 hydrochloride (Compound (±) 1) is an irreversible LSD1/KDM1A inhibitor with an IC₅₀ of 29 nM against hLSD1. LSD1-IN-49 hydrochloride irreversibly inhibits the enzymatic activity of LSD1 by forming an adduct with flavin adenine dinucleotide (FAD) in the binding pocket of LSD1. LSD1-IN-49 hydrochloride is applicable to research related to schizophrenia, autism spectrum disorder and Huntington's disease.