KDM4 Inhibitor

IOX1, a chemical probe, is a potent broad‐spectrum inhibitor of 2OG oxygenases, including the JmjC demethylases. IOX1 inhibits KDM4C, KDM4E, KDM2A, KDM3A and KDM6B with IC₅₀ values of 0.6 μM, 2.3 μM, 1.8 μM, 0.1 μM and 1.4 μM, respectively. IOX1 also inhibits ALKBH5.

JIB-04 is a pan-selective Jumonji histone demethylase inihibitor with IC₅₀s of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively.

QC6352 is an orally active KDM4 inhibitor with anti-tumor and anti-proliferative activity. QC6352 has in vivo inhibitory effects on PDX models of breast and colon cancer and reduces the number of chemoresistant cell populations. QC6352 inhibits KDM4 different isoforms with IC₅₀s of 104 nM (KDM4A), 56 nM (KDM4B), 35 nM (KDM4C), and 104 nM (KDM4D), respectively. QC6352 has moderate inhibitory activity against KDM5 with an IC₅₀ of 750 nM (KDM5B).

ML324 is a potent JMJD2 demethylase inhibitor with antiviral activity. ML324 also exhibits inhibition for the histone demethylase KDM4B, with an IC₅₀ of 4.9 μM. ML324 has potent anti-viral activity against both herpes simplex virus (HSV) and human cytomegalovirus (hCMV) infection via inhibition viral IE gene expression.

Zavondemstat (QC8222 free base; TACH 101 free base) 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 induces cell apoptosis, causes S-phase cell cycle arrest, reduces the population of tumor-initiating cells and inhibits cancer cell proliferation. Zavondemstat suppresses tumor growth and induces tumor regression in mouse xenograft models. Zavondemstat can be used for the research of various cancers including colorectal cancer, esophageal squamous cell carcinoma and triple-negative breast cancer.

KDM4C-IN-2 is a histone lysine demethylase KDM4C (JMJD2C) inhibitor with an IC₅₀ of 147 μM and a K_i of 51 μM. KDM4C-IN-2 can be used for the research of cancer, such as prostate and breast cancer.

KDM2/7-IN-1 (TC-E 5002) is a selective histone demethylase KDM2/7 subfamily inhibitor (IC₅₀ values are 0.2, 1.2, 6.8, 55, 83, >100 and >120 μM for KDM7A, KDM7B, KDM2A, KDM5A, KDM4C, KDM6A and KDM4A respectively). KDM2/7-IN-1 inhibits growth of HeLa and KYSE-150 cancer cells in vitro.

NCGC00244536 is a potent KDM4B inhibitor with an IC₅₀ of 10 nM.

KDM4C-IN-1 is a histone lysine demethylase KDM4C inhibitor with an IC₅₀ of 8 nM. KDM4C-IN-1 inhibits cancer cell proliferation. KDM4C-IN-1 can be used in the research of hepatocellular carcinoma and adenocarcinoma alveolar basal epithelial carcinoma.

KDM4D-IN-1 is a new histone lysine demethylase 4D (KDM4D) inhibitor with an IC₅₀ value of 0.41±0.03 μM.

KDM4-IN-3 (Compound 15) is a KDM4 inhibitor (IC₅₀ = 871 nM) that exhibits improved potency in biochemical assays. KDM4-IN-3 is cell-permeable and kills prostate cancer cells at low micro molar concentrations. KDM4-IN-3 inhibits growth of prostate cancer cell lines and increases the H3K9me3 abundance. KDM4-IN-3 can be studied in research for prostate cancer.

NCGC00247743 is a histone lysine demethylase KDM4 inhibitor.

KDM4-IN-2 (Compound 19a) is a potent and selective KDM4/KDM5 dual inhibitor with K_is of 4 and 7 nM for KDM4A and KDM5B, respectively.

NCDM-32B is a potent and selective KDM4 inhibitor, with IC₅₀ values of 3.0 μM for KDM4A and 1.0 μM for KDM4C in in vitro enzyme assays. NCDM-32B specifically increases global H3K9me3/me2 levels in basal breast cancer cells. NCDM-32B impairs the viability of KDM4C-amplified basal breast cancer cell lines (HCC1954 and Colo824). NCDM-32B can be used for the study of breast cancer.

KDM4-IN-4 (compound 47) is a potent histone lysine demethylase 4 (KDM4) inhibitor with a modest affinity binding to ~80 μM for KDM4A-Tudor domain. KDM4-IN-4 can inhibit H3K4Me3 binding to the Tudor domain in cells with an EC₅₀ value of 105 μM. KDM4-IN-4 can be used for researching anticancer.

EPZ020809 is a competitive KDM4C inhibitor with a K_i of 31 nM.