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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HDAC3-IN-T247
0 ImagesHDAC3-IN-T247 is a potent and selective HDAC3 (histone deacetylase 3) inhibitor, with an IC50 of 0.24 µM. HDAC3-IN-T247 induces a selective increase of NF-κB acetylation in HCT116 cells. HDAC3-IN-T247 shows anticancer and antiviral activity. HDAC3-IN-T247 inhibits growth of cancer cells, and activates HIV gene expression in latent HIV-infected cells.
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Bavarostat
0 ImagesSynonyms: EKZ-001Bavarostat (EKZ-001) is a blood-brain barrier-permeable, potent HDAC6 inhibitor and PET radiotracer, with an IC50 as low as 17 nM against human HDAC6. Bavarostat can be labeled with 18F and used as a probe to map HDAC6 distribution and measure target occupancy in the brains of non-human primates. Bavarostat also selectively modulates tubulin acetylation, but not histone acetylation. Bavarostat is applicable for research on Alzheimer's disease, other neurodegenerative disorders, and cancers.
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HDAC4-IN-1
0 ImagesHDAC4-IN-1 (compound 1a) is a class IIa HDACI inhibitor (IC50=0.077 μM). HDAC4-IN-1 can enhance Caspase-induced Apoptosis. HDAC4-IN-1 has anticancer activity. HDAC4-IN-1 can be used in the research of drug combination against cancer.
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HDAC-IN-53
0 ImagesCat. No.: HY-149208CAS No.: 2921948-27-6HDAC-IN-53 is an orally active, and selective HDAC1-3 inhibitor with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. HDAC-IN-53 does not inhibit class II HDACs (HDAC4, 5, 6, 7, 9; IC50>10 μM). HDAC-IN-53 induces caspase-dependent apoptosis. HDAC-IN-53 significantly inhibits the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice bearing MC38 colon cancer.
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XSJ-10
0 ImagesCat. No.: HY-157740XSJ-10 is a HDAC inhibitor containing a RAS/RAF protein interfering unit, with IC50s of 0.05 and 0.04 μM in PANC-1 cells and HT-29 cells. XSJ-10 can effectively induce the apoptosis of cancer cells and suppress the tumor by strongly inhibiting the RAS-RAF-MEK-ERK signaling pathway and the acetylation level of HDAC3.
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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-5
0 ImagesCat. No.: HY-146678CAS No.: 2413603-15-1HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC50 of 0.025 μM. HDAC6-IN-5 exhibits strong inhibitory activity against Aβ1-42 self-aggregation and AChE, with IC50 values of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.
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HDAC6-IN-6
0 ImagesCat. No.: HY-146679CAS No.: 2413603-10-6HDAC6-IN-6 (compound 6a) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC50 of 0.025 μM. HDAC6-IN-6 exhibits strong inhibitory activity against Aβ1-42 self-aggregation and AChE, with IC50 values of 3.0 and 0.72 μM. HDAC6-IN-6 can enhance neurite outgrowth without significant neurotoxicity.
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HDAC8-IN-6
0 ImagesCat. No.: HY-163143CAS No.: 3036403-81-0HDAC8-IN-6 (compound 3) is a potent HDAC8 inhibitor with an IC50 of 5.1 μM. HDAC8-IN-6 shows cytotoxicity.
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HDAC-IN-36
0 ImagesCat. No.: HY-146684CAS No.: 2482992-54-9
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TNI-97
0 ImagesCat. No.: HY-175030CAS No.: 2790425-52-2TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC50 of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.
