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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Romidepsin
0 ImagesSynonyms: FK 228; FR 901228; NSC 630176Romidepsin (FK 228) is a Histone deacetylase (HDAC) inhibitor with anti-tumor activities. Romidepsin (FK 228) inhibits HDAC1, HDAC2, HDAC4, and HDAC6 with IC50s of 36 nM, 47 nM, 510 nM and 1.4 μM, respectively. Romidepsin (FK 228) is produced by Chromobacterium violaceum, induces cell G2/M phase arrest and apoptosis.
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Tasquinimod
0 ImagesSynonyms: ABR-215050
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Quisinostat
0 ImagesSynonyms: JNJ-26481585
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HDAC4 ligand-2
0 ImagesCat. No.: HY-W039803CAS No.: 340736-76-7
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PROTAC HDAC4 Degrader-2
0 ImagesCat. No.: HY-184524CAS No.: 3035189-46-6PROTAC HDAC4 Degrader-2 is a class IIa selective negative control for HDAC4 PROTAC degraders, with an IC50 of 0.15 μM against HDAC4 and a cellular IC50 of 0.18 μM. PROTAC HDAC4 Degrader-2 fails to effectively recruit the VHL E3 ligase, and thus does not induce significant degradation of HDAC4 protein.
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HDAC6-IN-79
0 ImagesCat. No.: HY-182747HDAC6-IN-79 is a HDAC6 inhibitor with an IC50 of 98.40 nM, and it also exhibits inhibitory activity against other HDAC subtypes (HDAC1: 639.0 nM, HDAC2: 798.9 nM, HDAC8: 865.7 nM, HDAC4: 1187 nM). HDAC6-IN-79 induces acetylation of α-tubulin and histone H3, reduces the viability of cancer cells, activates the autophagy pathway and induces apoptosis. HDAC6-IN-79 can be used for research related to urothelial carcinoma (bladder cancer).
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Givinostat
0 ImagesSynonyms: ITF-2357
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Tubacin
0 ImagesTubacin is a potent and selective inhibitor of HDAC6, with an IC50 value of 4 nM and approximately 350-fold selectivity over HDAC1. Tubacin also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).
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Pracinostat
0 ImagesSynonyms: SB939Pracinostat is a potent histone deacetylase (HDAC) inhibitor, with IC50s of 40-140 nM, used for cancer research. Pracinostat also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2) hydrolase activity with an EC50 below 10 nM.
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Givinostat hydrochloride monohydrate
0 ImagesSynonyms: ITF-2357 hydrochloride monohydrate
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Quisinostat dihydrochloride
0 ImagesSynonyms: JNJ-26481585 dihydrochlorideQuisinostat dihydrochloride (JNJ-26481585 dihydrochloride) is an orally active, potent pan-HDAC inhibitor with IC50s of 0.11 nM, 0.33 nM, 0.64 nM, 0.46 nM, and 0.37 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11, respectively. Quisinostat dihydrochloride has a broad spectrum antitumoral activity. Quisinostat dihydrochloride can induce autophagy in neuroblastoma cells.
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BML-210
0 ImagesBML-210 is a potent HDAC inhibitor. BML-210 can inhibit the HDAC4-VP16-driven reporter signal with an apparent IC50 of ∼5 µM. BML-210 has a specific disruptive effect on the HDAC4:MEF2 interaction. BML-210 causes an increase in the G0/G1 phase. BML-210 induces apoptosis and displays antitumour activities in orthotopic mammary tumours in mice.
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CHDI-390576
0 ImagesSynonyms: CHDI00390576CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor with IC50s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform.
