HDAC4
HDAC4 is a class IIa histone deacetylase that acts as a signal-dependent transcriptional regulator linking extracellular cues to chromatin remodeling, gene expression, and cell differentiation[1][2]. Mechanistically, class IIa HDACs, including HDAC4, shuttle between nuclear and cytoplasmic compartments through post-translational modification, and this localization controls their transcriptional functions[3]. In liver, HDAC4, HDAC5, and HDAC7 respond to glucagon by entering the nucleus, associating with gluconeogenic promoters, recruiting HDAC3, activating FOXO transcription factors, and increasing blood-glucose-related gene expression[4]. In skeletal muscle, class II HDAC proteins repress MEF2 activity and suppress slow-twitch oxidative myofiber formation, while MEF2 activation promotes endurance-associated fiber programs[5]. In pancreatic endocrine models, HDAC4, HDAC5, and HDAC9 regulate β-cell and δ-cell lineage control, and class IIa HDAC inhibition with MC1568 amplifies endocrine β- and δ-cells[6]. Compared with related isoforms, HDAC4 belongs to the HDAC4/5/7/9 class IIa subgroup, which shares MEF2-related transcriptional partners but shows distinct disease-linked regulatory roles[7]. For experimental applications, LBH589 confined HDAC4 to the cytoplasm, prolonged γ-H2AX foci after irradiation, and sensitized non-small cell lung cancer models to radiation-induced DNA double-strand breaks[8]. Selective inhibitor design also identified LMK235 as showing nanomolar inhibition of HDAC4 and HDAC5, unlike vorinostat and TSA, which inhibited these isoforms in the higher micromolar range[9].
References:
- [1]. Verdin E, et al. Class II histone deacetylases: versatile regulators. Trends Genet. 2003 May;19(5):286-93. [Content Brief]
- [2]. Yang XJ, et al. Class II histone deacetylases: from sequence to function, regulation, and clinical implication. Mol Cell Biol. 2005 Apr;25(8):2873-84. [Content Brief]
- [3]. Mathias RA, et al. Post-translational modifications regulate class IIa histone deacetylase (HDAC) function in health and disease. Mol Cell Proteomics. 2015 Mar;14(3):456-70. [Content Brief]
- [4]. Mihaylova MM, et al. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell. 2011 May 13;145(4):607-21. [Content Brief]
- [5]. Potthoff MJ, et al. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest. 2007 Sep;117(9):2459-67. [Content Brief]
- [6]. Lenoir O, et al. Specific control of pancreatic endocrine β- and δ-cell mass by class IIa histone deacetylases HDAC4, HDAC5, and HDAC9. Diabetes. 2011 Nov;60(11):2861-71. [Content Brief]
- [7]. Clocchiatti A, et al. Class IIa HDACs: from important roles in differentiation to possible implications in tumourigenesis. J Cell Mol Med. 2011 Sep;15(9):1833-46. [Content Brief]
- [8]. Geng L, et al. Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res. 2006 Dec 1;66(23):11298-304. [Content Brief]
- [9]. Marek L, et al. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 2013 Jan 24;56(2):427-36. [Content Brief]
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HDAC4 Related Products (72)
Related Products (72)
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Antibodies (2)
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HDAC8-IN-3
0 ImagesCat. No.: HY-147934CAS No.: 2432825-93-7
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PI3K/HDAC-IN-2
0 ImagesCat. No.: HY-146159CAS No.: 2361418-65-5PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC50s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC50s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.
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HDACs/EZH2-IN-1
0 ImagesCat. No.: HY-169400HDACs/EZH2-IN-1 (Compound 22a) is a HDACs/EZH2 inhibitor (EZH2 Y641N inhibition rate at 50 nM: 98%), with selective inhibition against HDAC1 and HDAC6 (IC50: 0.23 μM and 0.07 μM, respectively). HDACs/EZH2-IN-1 exerts a antiproliferative effect on diffuse large B-cell lymphoma cells harboring an EZH2 mutation and on various acute myeloid leukemia cells. HDACs/EZH2-IN-1 has the ability to induce cell differentiation and Apoptosis.
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SM-06-09
0 ImagesCat. No.: HY-184203SM-06-09 is a potent, highly selective, orally active tetrazolone-based HDAC6 inhibitor with an IC50 value of 0.49 nM. SM-06-09 promotes tumor-associated macrophage (TAM) polarization toward an antitumor M1-like phenotype and enhances macrophage phagocytosis, antigen presentation, and T-cell activation. SM-06-09 remodels the tumor immune microenvironment, exhibits antitumor activity in melanoma models, and enhances the efficacy of anti-PD-1 immune checkpoint blockade.
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HDAC6-IN-10
0 ImagesCat. No.: HY-150595CAS No.: 2408286-73-5HDAC6-IN-10 is a highly selective HDAC6 inhibitor with the IC50 of 0.73 nM. HDAC6-IN-10 has 144~10941-fold selectivity over other HDAC isoforms. HDAC6-IN-10 shows anti-proliferative activities against multiple myeloma cells.
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HDAC-IN-105
0 ImagesCat. No.: HY-184705HDAC-IN-105 is a histone deacetylase (HDAC) inhibitor with binding to HDAC2 and HDAC4 isoforms. HDAC-IN-105 suppresses HDAC activity via binding within conserved HDAC catalytic pockets. HDAC-IN-105 induces G2/M phase cell cycle arrest. HDAC-IN-105 triggers mitochondrial dysfunction marked by loss of mitochondrial membrane potential. HDAC-IN-105 exhibits growth inhibition in triple-negative breast cancer cells and low toxicity toward normal cells. HDAC-IN-105 can be used for the research of triple-negative breast cancer.
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MC2590
0 ImagesMC2590 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2590 is a inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) with IC50s of 0.015 μM-0.156 μM. MC2590 also inhibits HDAC isoforms HDAC4, HDAC5, HDAC7, HDAC9, HDAC11 with IC50s of 1.35 μM-3.98 μM. MC2625 induces G2/M cell cycle arrest and modulates pro- and anti-apoptotic microRNAs towards apoptosis induction.
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HDAC6 ligand-7
0 ImagesCat. No.: HY-179227HDAC6 ligand-7 (Compound 16a) is a positron emission tomography (PET) tracer for the deacetylase 6 (HDAC6) enzyme with a Kd value of 1.66 nM. HDAC6 ligand-7 exhibits excellent HDAC6 inhibitory activity, with IC50 values of 2.7 and 3.7 nM for hHDAC6 and mHDAC6, respectively, and has high selectivity for HDAC1/4/7/8. HDAC6 ligand-7 after being radioactively labeled with fluorine-18, [¹⁸F]HDAC6 ligand-7 shows varying degrees of radioactive uptake in PET, which can reflect the specific binding to HDAC6. HDAC6 ligand-7 can be used for the study of HDAC6 imaging.
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C1A
0 ImagesCat. No.: HY-124946CAS No.: 1021463-02-4
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FLT3/HDAC-IN-3
0 ImagesCat. No.: HY-181086CAS No.: 2864394-30-7FLT3/HDAC-IN-3 is a dual inhibitor of FLT3 and HDAC. FLT3/HDAC-IN-3 potently inhibits FLT3 (IC50 = 14 nM), HDAC1 (IC50 = 27 nM), HDAC6 (IC50 = 20 nM), and FLT3D853Y (IC50 = 55 nM), exhibits weak activity against HDAC8, and shows no activity against HDAC4. FLT3/HDAC-IN-3 possesses kinase selectivity, plasma stability, and stability in human liver microsomes. FLT3/HDAC-IN-3 demonstrates anti-proliferative effects in a variety of hematological malignancy cell lines. FLT3/HDAC-IN-3 shows efficacy in the Jeko-1 xenograft model without observed significant toxicity. FLT3/HDAC-IN-3 can be used in the study of hematological malignancies.
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PROTAC HDAC4 Degrader-1
0 ImagesCat. No.: HY-179321CAS No.: 3036245-14-1PROTAC HDAC4 Degrader-1 (compound SCT-1) is a potent and selective PROTAC HDAC4 degrader. PROTAC HDAC4 Degrader-1 reduces HDAC4 protein level, induces S phase cell cycle arrest, and inhibits cell colony formation, thereby inhibiting proliferation of the tumor cells. PROTAC HDAC4 Degrader-1 exhibits efficacy in a H460 mouse model. PROTAC HDAC4 Degrader-1 can be used for cancer research, such as lung cancer.
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MC2625
0 ImagesCat. No.: HY-152225CAS No.: 1776116-75-6MC2625 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2625 show selective HDAC3 and HDAC6 inhibition with IC50s of 80 nM and 11 nM. MC2625 increases acetyl-H3 and acetyl-tubulin levels and inhibits cancer stem cells (CSCs) growth by apoptosis induction.
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HDAC6-IN-69
0 ImagesCat. No.: HY-180214HDAC6-IN-69 is a brain-penetrant and highly selective HDAC6 inhibitor with an IC50 of 4.0 nM. HDAC6-IN-69 shows >176-fold against other HDAC isoforms. HDAC6-IN-69 engages the target in neuronal cells by dose-dependently upregulating acetylated α-tubulin in virto. HDAC6-IN-69 has neuroprotective effect and can be used for ischemic stroke research .
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Rodin-C
0 ImagesCat. No.: HY-176868CAS No.: 2065162-16-3Rodin-C is a selective HDAC inhibitor with IC50s of 0.059, 0.18 and 5.39 μM for HDAC1, HDAC2 and HDAC11, respectively, over HDAC3-10. Rodin-C significantly inhibits the HDAC-CoREST complex with low hematological toxicity. Rodin-C can be used for neurologic disorders such as Alzheimer’s disease research.
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HDAC6-IN-82
0 ImagesCat. No.: HY-183560CAS No.: 1228571-33-2HDAC6-IN-82 is a selective HDAC6 inhibitor with an IC50 of 4.9 nM against HDAC6. HDAC6-IN-82 inhibits HDAC1 (112 nM), HDAC2 (737 nM), HDAC3 (623 nM), HDAC8 (1140 nM), HDAC10 (91.4 nM) and HDAC11 (219 nM). HDAC6-IN-82 reduces cancer cell viability, induces cell cycle arrest, triggers apoptosis, and increases the acetylation levels of H3K9 and α-tubulin. HDAC6-IN-82 can be used in cancer-related research such as leukemia.
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FF2039
0 ImagesCat. No.: HY-172159FF2039 is a pan-HDAC PROTAC degrader that binds to DCAF11, acting on HDAC6, HDAC1, HDAC2 and HDAC4. FF2039 recruits the DCAF11 E3 ligase and mediates the polyubiquitination and degradation of HDACs via the ubiquitin-proteasome system. FF2039 induces cell cycle arrest, apoptosis, cytotoxicity and antiproliferative activity in cancer cells, and reduces the clonogenic capacity of cancer cells. FF2039 is applicable to research related to multiple myeloma, triple-negative breast cancer and glioblastoma.
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KH-259
0 ImagesCat. No.: HY-150503CAS No.: 3023019-93-1
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PIM-1/HDAC-IN-2
0 ImagesCat. No.: HY-174302CAS No.: 3103925-33-0PIM-1/HDAC-IN-2 is a robust PIM/HDAC inhibitor (IC50 = 0.11 μM in MV4-11cells), which exerts a synergistic antiproliferative effect through a dual mechanism of inhibiting PIM1 kinase and selectively inhibiting HDAC6. PIM-1/HDAC-IN-2 induces cell apoptosis. PIM-1/HDAC-IN-2 remarkably induces the cleavage of PARP, thereby initiating the arrest of the cell cycle in G1 phase and a reduction in S phase. PIM-1/HDAC-IN-2 demonstrates significant anticancer efficacyin the MV4-11 xenograft model without notable toxicity[1].
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G4/HDAC-IN-1
0 ImagesCat. No.: HY-151263CAS No.: 3031784-60-5G4/HDAC-IN-1 (compound a6) is a G4/HDAC dual-targeting compound. G4/HDAC-IN-1 inhibits intracellular HDAC activity with an IC50 value of 1.1 μM, and induces G4 formation. G4/HDAC-IN-1 inhibits TNBC proliferation and tumor growth in TNBC xenograft model. G4/HDAC-IN-1 can be used for the research of cancer.
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HDAC6-IN-63
0 ImagesCat. No.: HY-178022HDAC6-IN-63 (Compound 7) is an orally active HDAC6 inhibitor with an IC50 of 145 nM. HDAC6-IN-63 inhibits the expression of Sp1 and RAD51, thereby inducing Caspase-dependent apoptosis. HDAC6-IN-63 has antitumor activity and sensitizes Etoposide (HY-13629) and Gemcitabine (HY-17026), promoting synergistic death of NSCLC cells through the inhibition of homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA DSB repair. HDAC6-IN-63 can be used for chemotherapy of cancers like NSCLC research.
