HDAC5

HDAC5 (histone deacetylase 5) is a member of the class IIa histone deacetylase family and functions as a signal-responsive transcriptional regulator through its conserved N-terminal transcription factor-binding domain and C-terminal catalytic domain^[1]^[2]. HDAC5 interacts with transcription factors such as myocyte enhancer factor 2 (MEF2), and phosphorylation-dependent binding to 14-3-3 proteins promotes its nuclear export, thereby relieving transcriptional repression of target genes^[1]^[2]. Mechanistically, HDAC5 participates in chromatin-dependent gene regulation and integrates extracellular signaling pathways that control cellular differentiation, survival, and tissue-specific transcriptional programs^[2]^[3]. These properties place HDAC5 within a broader class IIa HDAC regulatory network that functions primarily through transcriptional repression complexes rather than strong intrinsic deacetylase activity^[2]. In disease-related settings, aberrant HDAC5 expression has been reported across multiple cancer types, where it is associated with regulation of cell proliferation, invasion, stemness maintenance, immune-related processes, and cell-cycle progression^[1]. Experimental studies summarized in cancer models further indicate that HDAC5 can influence oncogenic pathways including DLL4, Notch1, c-Met, and Six1 signaling, supporting its relevance as a molecular regulator of tumor biology^[1]. Compared with related HDAC isoforms, HDAC5 shares the characteristic class IIa adaptor architecture and signal-dependent nucleocytoplasmic shuttling mechanism, yet retains distinct tissue distribution patterns and target-gene regulatory functions that contribute to biological specificity^[1]^[2]. For experimental applications, HDAC5 is widely investigated as a candidate therapeutic target, and ongoing efforts to develop class IIa-selective HDAC modulators aim to improve isoform selectivity while minimizing off-target effects associated with pan-HDAC inhibition^[2]^[3].

References:

[1]. Yang J, et al. Insights Into the Function and Clinical Application of HDAC5 in Cancer Management. Front Oncol. 2021 Jun 10;11:661620. [Content Brief]

[2]. Park SY, et al. A short guide to histone deacetylases including recent progress on class II enzymes. Exp Mol Med. 2020 Feb;52(2):204-212. [Content Brief]

[3]. Ujlaky-Nagy L, et al. Disrupting EGFR-HER2 Transactivation by Pertuzumab in HER2-Positive Cancer: Quantitative Analysis Reveals EGFR Signal Input as Potential Predictor of Therapeutic Outcome. Int J Mol Sci. 2024 May 29;25(11):5978. [Content Brief]

HDAC5 Related Products (56):

By Type:	Pan (44) Selective (3)
By Effects:	Inhibitors (55) Activator (1)

Cat. No.	Product Name	Effect	Purity

HY-16026

Ricolinostat	Inhibitor	99.83%
Ricolinostat (ACY-1215) is a potent and selective HDAC6 inhibitor, with an IC₅₀ of 5 nM. ACY-1215 also inhibits HDAC1, HDAC2, and HDAC3 with IC₅₀s of 58, 48, and 51 nM, respectively.

HY-15433

Quisinostat	Inhibitor	99.71%
Quisinostat (JNJ-26481585) is a potent and orally active pan-HDAC inhibitor (HDACi), with IC₅₀ values ranging from 0.11 nM to 0.64 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11. Quisinostat has a broad spectrum antitumoral activity. Quisinostat can induce autophagy in neuroblastoma cells.

HY-18361

TMP195	Inhibitor	99.82%
TMP195 is a selective class IIa histone deacetylase (HDAC) inhibitor with K_is of 59, 60, 26, 15 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively.

HY-14842

Givinostat	Inhibitor	98.67%
Givinostat (ITF-2357) is a HDAC inhibitor with an IC₅₀ of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat can be used for Duchenne muscular dystrophy (DMD) research. Givinostat can penetrate the blood-brain barrier (BBB).

HY-13428

Tubacin	Inhibitor
Tubacin 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).

HY-181126

G194-0712	Activator	99.82%
G194-0712 is a selective histone deacetylase 5 (HDAC5) activator with an EC₅₀ of 7.96 μM and a K_d of 2.53 μM. G194-0712 restores ACTN4-K417 deacetylation and nuclear import, and increases CSTA expression. G194-0712 accelerates wound closure in chronic wound models, reducing wound area and epithelial gap. G194-0712 can be used for the research of chronic skin wounds, such as diabetic wounds, ischemic wounds, radiation injury wounds.

HY-P10462A

SAP15 acetate	Inhibitor	98.04%
SAP15 (Synthetic anti-inflammatory peptide 15) acetate is a synthetic anti-inflammatory peptide consisting of 15 amino acids designed from human beta-defensin 3. SAP15 acetate has the ability to penetrate cells and is able to induce downregulation of intracellular inflammation. SAP15 acetate inhibits inflammation by inhibiting the phosphorylation of HDAC5 and thereby reducing the phosphorylation of NF-κB p65. SAP15 acetate inhibits HDAC5 and NF-κB p65 phosphorylation in LPS (HY-D1056)-induced macrophages. SAP15 acetate increases the expression of aggrecan and type II collagen and decreases the expression of osteocalcin in LPS-induced chondrocytes. SAP15 acetate can be used in the study of inflammation regulation and anti-inflammatory therapy of biomaterials.

HY-184203

SM-06-09	Inhibitor
SM-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.

HY-13522

Fimepinostat	Inhibitor	99.95%
Fimepinostat (CUDC-907) potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes with an IC₅₀ of 19/54/39 nM and 1.7/5.0/1.8/2.8 nM for PI3Kα/PI3Kβ/PI3Kδ and HDAC1/HDAC2/HDAC3/HDAC10 , respectively.

HY-18998

LMK-235	Inhibitor	99.61%
LMK-235 is a potent and selective HDAC4/5 inhibitor, inhibits HDAC5, HDAC4, HDAC6, HDAC1, HDAC2, HDAC11 and HDAC8, with IC₅₀s of 4.22 nM, 11.9 nM, 55.7 nM, 320 nM, 881 nM, 852 nM and 1278 nM, respectively, and is used in cancer research.

HY-18360

TMP269	Inhibitor	98.16%
TMP269 is a novel and selective class IIa histone deacetylase (HDAC) inhibitor with IC₅₀s of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively.

HY-13322

Pracinostat	Inhibitor	99.80%
Pracinostat 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.

HY-10223

CUDC-101	Inhibitor	99.05%
CUDC-101 is a potent inhibitor of HDAC, EGFR, and HER2 with IC₅₀s of 4.4, 2.4, and 15.7 nM, respectively. CUDC-101 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

HY-16699

Nexturastat A	Inhibitor	98.69%
Nexturastat A is a potent, selective HDAC6 inhibitor. Nexturastat A has inhibitory for HDAC6 with an IC₅₀ of 5 nM. Nexturastat A can be used for the research of multiple myeloma (MM).

HY-14842B

Givinostat hydrochloride monohydrate	Inhibitor	99.63%
Givinostat hydrochloride monohydrate (ITF-2357 hydrochloride monohydrate) is a HDAC inhibitor with an IC₅₀ of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride monohydrate can penetrate the blood-brain barrier (BBB).

HY-15433A

Quisinostat dihydrochloride	Inhibitor	99.05%
Quisinostat 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.

HY-16012A

Domatinostat	Inhibitor	99.34%
Domatinostat (4SC-202 free base) is a selective class I HDAC inhibitor with IC₅₀ of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. It also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).

HY-119939

CHDI-390576	Inhibitor	98.10%
CHDI-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.

HY-112719

BRD 4354	Inhibitor	98.10%
BRD 4354 is a moderately potent inhibitor of HDAC5 and HDAC9, with IC₅₀s of 0.85 and 1.88 μM, respectively.

HY-126330

SS-208	Inhibitor	99.00%
SS-208 is a selective HDAC6 inhibitor, with an IC₅₀ of 12 nM. SS-208 possesses anti-tumor activity in melanoma.

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