2. Signaling Pathways
  3. Epigenetics
  4. Histone Demethylase
  5. KDM5 Isoform

KDM5

KDM5 (lysine demethylase 5) proteins comprise the KDM5A, KDM5B, KDM5C, and KDM5D isoforms, which function as Fe(II)- and α-ketoglutarate-dependent histone demethylases that remove methyl groups from H3K4me2/3 and thereby regulate chromatin state and transcriptional programs[1][2]. Mechanistically, KDM5 family members act as context-dependent transcriptional regulators that can either activate or repress gene expression, linking histone methylation dynamics to cellular differentiation, proliferation, and developmental processes[3]. Dysregulation of KDM5 signaling has been widely associated with tumor initiation, progression, and therapeutic resistance, highlighting the importance of this epigenetic pathway in cancer biology[4][5][6]. In disease models, KDM5A and KDM5B have been implicated in the regulation of proliferation, angiogenesis, DNA repair, metastasis, and drug-tolerant cellular states across multiple cancer types[4][6][7]. Compared with related isoforms, KDM5A and KDM5B share high sequence homology and domain architecture but exhibit distinct target-gene specificity and gene-regulatory functions, whereas KDM5C lacks the PHD3 domain and is frequently linked to neurodevelopmental disorders and tumor-suppressive activities in selected cancers[5][8]. KDM5D, encoded on the Y chromosome, participates in physiological processes including spermatogenesis and differentiation and displays disease associations distinct from other KDM5 members[8]. For experimental applications, small-molecule KDM5 inhibitors have been developed to modulate KDM5 enzymatic activity, and KDM5 inhibition has demonstrated antitumor effects in cellular and in vivo models, supporting the use of KDM5 proteins as research targets for epigenetic regulation and therapeutic response studies[9][10].

KDM5 Related Products (18):

Cat. No. Product Name Effect Purity
  • HY-100421
    CPI-455
    		Inhibitor 98.95%
    CPI-455 is a specific, pan-KDM5 inhibitor with an IC50 of 10 nM for KDM5A. CPI-455 mediates KDM5 inhibition, elevates global levels of H3K4me3, and decreases the number of drug-tolerant persister cancer cells in multiple cancer cell line models treated with standard chemotherapy or targeted agents.
  • HY-13953
    JIB-04
    		Inhibitor 98.63%
    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.
  • HY-104048
    QC6352
    		Inhibitor 99.13%
    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).
  • HY-120400
    KDM5-C70
    		Inhibitor 98.82%
    KDM5-C70 is an ethyl ester derivative of KDM5-C49 and a potent, cell-permeable and pan-KDM5 histone demethylase inhibitor. KDM5-C70 has an antiproliferative effect in myeloma cells, leading to genome-wide elevation of H3K4me3 levels.
  • HY-102047B
    KDOAM-25 citrate
    		Inhibitor 98.56%
    KDOAM-25 citrate is a potent and highly selective histone lysine demethylases 5 (KDM5) inhibitor with IC50s of 71 nM, 19 nM, 69 nM, 69 nM for KDM5A, KDM5B, KDM5C, KDM5D, respectively. KDOAM-25 citrate increases global H3K4 methylation at transcriptional start sites and impairs proliferation in multiple myeloma MM1S cells.
  • HY-183618
    DW-229
    		Degrader
    DW-229 is a PROTAC degrader derived from Deferiprone (HY-B0568), targeting Fe(II)/α‑ketoglutarate‑dependent histone lysine demethylases (KDMs). DW-229 degrades KDM2A, KDM3A, KDM5B, KDM4A‑C, KDM5C, KDM6B in breast cancer cells. DW-229 shows IC50 < 0.5 μM against MCF‑7 cells and IC50 of 8.87 μM against MDA‑MB‑231 cells, with high cancer cell selectivity. DW-229 can be used for the research of breast cancer, liver cancer, prostate cancer, lung cancer.
  • HY-136682
    N19-0881
    		Inhibitor
    N19-0881 (Compound 33) is an orally active, potent and selective KDM5A/5B histone lysine demethylase inhibitor (IC50= 0.013 μM and 0.002 μM, respectively). N19-0881 is promising for research of epigenetically dysregulated tumors (e.g., breast cancer).
  • HY-100744
    AS8351
    		Inhibitor 99.88%
    AS8351 (NSC51355) is a KDM5B inhibitor, which can induce and sustain active chromatin marks to facilitate the induction of cardiomyocyte-like cells.
  • HY-116761
    GSK467
    		Inhibitor 99.34%
    GSK467 is a cell penetrant and selective KDM5B (JARID1B or PLU1) inhibitor with a Ki of 10 nM and an IC50 of 26 nM. GSK467 shows 180-fold selectivity for KDM4C and no measurable inhibitory effects toward KDM6 or other Jumonji family members.
  • HY-151483
    TK-129
    		Inhibitor ≥98.0%
    TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity; IC50=44 nM). TK-129 exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. TK-129 reduces ang II-induced activation of cardiac fibroblasts in vitro and reduces isoprenaline-induced myocardial remodelling and fibrosis in vivo. TK-129 can be used in studies of cardiovascular disease.
  • HY-100014
    KDM5A-IN-1
    		Inhibitor 99.64%
    KDM5A-IN-1 is a potent, orally bioavailable pan-histone lysine demethylases 5 (KDM5) inhibitor with IC50s of 45 nM, 56 nM and 55 nM for KDM5A, KDM5B and KDM5C, respectively, and with an EC50 value of 960 nM for PC9 H3K4Me3. KDM5A-IN-1 is significantly less potent against other KDM5B enzymes (1A, 2B, 3B, 4C, 6A, 7B).
  • HY-100421A
    CPI-455 hydrochloride
    		Inhibitor 99.95%
    CPI-455 hydrochloride is a specific, pan-KDM5 inhibitor with an IC50 of 10 nM for KDM5A. CPI-455 hydrochloride mediates KDM5 inhibition, elevates global levels of H3K4me3, and decreases the number of drug-tolerant persister cancer cells in multiple cancer cell line models treated with standard chemotherapy or targeted agents.
  • HY-138691A
    JQKD82 trihydrochloride
    		Inhibitor 99.89%
    JQKD82 (JADA82) trihydrochloride is a cell-permeable and selective KDM5 inhibitor. JQKD82 trihydrochloride increases H3K4me3 and can be used for the research of multiple myeloma.
  • HY-100422
    KDM5-IN-1
    		Inhibitor 99.52%
    KDM5-IN-1 is a potent, selective and orally bioavailable KDM5 inhibitor with an IC50 of 15.1 nM.
  • HY-101451
    PBIT
    		Inhibitor 99.13%
    PBIT is a specific inhibitor of the Jumonji AT-rich Interactive Domain 1 (JARID1) enzymes. PBIT inhibits JARID1B (KDM5B or PLU1) histone demethylase with an IC50 of about 3 μM . PBIT also inhibits JARID1A and JARID1C with IC50s of 6 μM and 4.9 μM, respectively.
  • HY-119397
    KDM5-C49
    		Inhibitor
    KDM5-C49 (KDOAM-20) is a potent and selective inhibitor of KDM5 demethylases, with IC50s of 40 nM, 160 nM, and 100 nM for KDM5A, KDM5B, and KDM5C enzymes, respectively. KDM5-C49 can be used for the research of cancer.
  • HY-175036
    YTHu78
    		Degrader
    YTHu78 is a KDM5B PROTAC-type degrader. YTHu78 induces KDM5B degradation via the ubiquitin-proteasome system and triggers apoptosis in MV-4-11 and MM.1S cell lines. YTHu78 exhibits significant antiproliferative activity against a variety of hematological cancer cell lines and can be used to study hematological cancers. (Pink: KDM5B ligand: (HY-116761); Blue: Thalidomide ligand: (HY-14658), Black + Pink: KDM5B ligand + linker: (HY-175145)).
  • HY-138691
    JQKD82
    		Inhibitor
    JQKD82 (JADA82) is a cell-permeable and selective KDM5 inhibitor. JQKD82 increases H3K4me3 and can be used for the research of multiple myeloma.