HDAC

Givinostat hydrochloride (ITF-2357 hydrochloride) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively.

Nanatinostat (CHR-3996) is a potent, class I selective and orally active histone deacetylase (HDAC) inhibitor with an IC50 of 8 nM.

Belinostat (PXD101; PX105684) is a potent HDAC inhibitor with an IC50 of 27 nM in HeLa cell extracts.

Sulforaphane activates Nrf2 and inhibits high glucose-induced progression of pancreatic cancer via AMPK dependent signaling. Sulforaphane has shown anti-cancer and anti-inflammatory activities.

BRD6688 is a selective inhibitor of HDAC2 that acts by enhancing the learning and memory processes.

BRD3308 is a highly selective HDAC3 inhibitor with an IC50 of 54 nM.

Tubastatin A is a potent HDAC6 inhibitor with an IC50 value of 15 nM.

Quisinostat dihydrochloride (JNJ-26481585 dihydrochloride) is an orally available, 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.

Suberoyl bis-hydroxamic acid (Suberohydroxamic acid; SBHA) is a competitive and cell-permeable HDAC1 and HDAC3 inhibitor with ID50 values of 0.25 μM and 0.30 μM, respectively.

Nullscript is an inactive analog of Scriptaid and serves as a negative control for Scriptaid, a representative histone deacetylase (HDAC) inhibitor. Despite its inactivity as an HDAC inhibitor, Nullscript inhibits the growth of *Cryptosporidium parvum* with an IC₅₀ value of 2.1 μM.

SGC-UBD253 is a potent antagonist of the HDAC6 ubiquitin-binding domain (UBD). It is suitable for use in cancer research.

Psammaplin A, a marine-derived metabolite, is a potent inhibitor of HDAC1 (IC50: 45 nM), DNA methyltransferases (IC50: 18.6 nM), and aminopeptidase N (IC50: 18 μM). It also suppresses DNA topoisomerase and farnesyl protein transferase activities. As a PPARγ activator, Psammaplin A induces apoptosis and exhibits antitumor, anti-inflammatory, and anti-angiogenic properties. Additionally, it demonstrates antibacterial activity against Gram-positive bacteria by inhibiting DNA synthesis and DNA

Elevenostat (JB3-22) is a selective histone deacetylase 11 (HDAC11) inhibitor with an IC₅₀ of 0.235 µM. It exhibits antitumor activity by inducing apoptosis in multiple myeloma cells and shows potential as a therapeutic agent in hematologic malignancies. Additionally, Elevenostat has been shown to inhibit the maturation of mouse oocytes, suggesting a role for HDAC11 in reproductive biology and offering a tool for studying epigenetic regulation in oocyte development.

Bufexamac is a nonsteroidal anti-inflammatory drug (NSAID) that functions as a dual inhibitor of class IIb histone deacetylases—HDAC6 and HDAC10—as well as leukotriene A4 hydrolase (LTA4H). It exhibits binding affinities (K\_d) of 0.53 µM for HDAC6 and 0.22 µM for HDAC10. Through its dual inhibitory activity, Bufexamac combines epigenetic modulation with anti-inflammatory effects, making it a valuable compound for research in inflammation, immune regulation, and HDAC-related pathologies.

TYA-018 is an orally active, potent, and highly selective inhibitor of histone deacetylase 6 (HDAC6). In preclinical studies, TYA-018 demonstrates cardioprotective effects by preserving heart function in mice. Additionally, it enhances systemic energetics by upregulating the expression of genes involved in fatty acid metabolism, protein turnover, and oxidative phosphorylation, highlighting its potential in both cardiovascular and metabolic disease research.

CYD19 is a potent dual-target inhibitor that simultaneously disrupts Snail and HDAC1 activity. It exhibits an IC₅₀ of 0.405 μM against HDAC1 and binds Snail with a K\_d of 0.18 μM. In HCT-116 colorectal cancer cells, CYD19 increases histone H4 acetylation and downregulates Snail protein expression, leading to the induction of apoptosis. This dual mechanism positions CYD19 as a promising therapeutic candidate for targeting epithelial–mesenchymal transition (EMT) and epigenetic dysregulation in cancer.

TNG260 is a selective and orally bioavailable inhibitor of histone deacetylase 1 (HDAC1) and the CoREST transcriptional corepressor complex. It exhibits approximately 10-fold selectivity for HDAC1 over HDAC3 and 500-fold selectivity for the CoREST complex compared to other HDAC-containing complexes such as NuRD and Sin3. TNG260 modulates the tumor immune microenvironment by reducing immunosuppressive neutrophil infiltration, enhancing effector T cell recruitment, and reversing anti-PD-1 resistance associated with STK11 mutations through inhibition of the CoREST–HDAC1 axis. In preclinical models, TNG260 induces durable tumor regression when combined with α-PD-1 therapy in MC38 tumor-bearing mice harboring STK11 mutations, while demonstrating reduced hematologic toxicity compared to non-selective HDAC inhibitors.

Rhamnetin is a naturally occurring flavonoid and quercetin derivative found in *Coriandrum sativum*. It functions as an inhibitor of secretory phospholipase A₂ and histone deacetylase 2 (HDAC2), contributing to its broad pharmacological profile. Rhamnetin exhibits notable antitumor, antioxidant, and anti-inflammatory activities, making it a promising compound for research in cancer, oxidative stress-related conditions, and inflammatory diseases.

DKFZ-748 is a selective histone deacetylase 10 (HDAC10) inhibitor with a pIC₅₀ of 7.66, corresponding to an IC₅₀ of approximately 22 nM. It exhibits antitumor activity, making it a valuable tool for studying HDAC10-mediated biological processes and a promising candidate for the development of targeted cancer therapies.

KA2507 is a potent, orally active, and highly selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 2.5 nM. It exhibits strong antitumor activity and immunomodulatory effects in preclinical models, making it a promising candidate for cancer therapy, particularly in tumors where HDAC6 plays a key role in tumor progression and immune evasion.

KR-39038 is a potent and orally bioavailable inhibitor of G protein-coupled receptor kinase 5 (GRK5), with an IC₅₀ of 0.02 μM. It effectively suppresses angiotensin II–induced cellular hypertrophy by inhibiting the HDAC5 signaling pathway in neonatal cardiomyocytes. KR-39038 exhibits strong anti-hypertrophic activity and improves cardiac function in preclinical models, making it a promising candidate for research in heart failure and related cardiovascular diseases.

T-518 is an orally active, selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 36 nM for human HDAC6. It is capable of crossing the blood–brain barrier, making it suitable for central nervous system applications. T-518 is particularly useful in tauopathy research, where HDAC6 inhibition may modulate tau pathology and neurodegenerative processes.

9-Hydroxyoctadecanoic acid (9-HSA) is a naturally derived inhibitor of histone deacetylase 1 (HDAC1), inhibiting approximately 66.4% of HDAC1 enzymatic activity at a concentration of 5 μM. It exhibits notable anticancer activity, likely through epigenetic modulation of gene expression, making it a promising compound for cancer research and therapeutic development targeting HDAC1-regulated pathways.

SE-7552 is an orally active, highly selective histone deacetylase 6 (HDAC6) inhibitor, based on a 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO) scaffold, with an IC₅₀ of 33 nM. As a non-hydroxamate HDAC6 inhibitor, SE-7552 demonstrates exceptional isoform selectivity, showing over 850-fold preference for HDAC6 compared to other HDAC isozymes. In preclinical studies, SE-7552 effectively inhibits multiple myeloma tumor growth in vivo and also exhibits anti-obesity effects in diet-induced obese mouse models, highlighting its therapeutic potential in both oncology and metabolic disease research.

Gnetol is a bioactive phenolic compound isolated from the root of *Gnetum montanum* with diverse pharmacological properties. It potently inhibits cyclooxygenase-1 (COX-1) with an IC₅₀ of 0.78 μM and exhibits histone deacetylase (HDAC) inhibitory activity. Gnetol is also a strong tyrosinase inhibitor, with an IC₅₀ of 4.5 μM against murine tyrosinase, leading to suppression of melanin biosynthesis. In addition to its antioxidant, antiproliferative, anticancer, and hepatoprotective effects, Gnetol modulates metabolic enzymes in a concentration-dependent manner, including α-amylase, α-glucosidase, and adipogenesis pathways, making it a promising candidate for research in oncology, dermatology, and metabolic disorders.

Marein is a natural compound with multifaceted pharmacological properties, including HDAC inhibition with an IC₅₀ of 100 μM. It exerts neuroprotective effects by preserving mitochondrial function and activating the AMPK signaling pathway. In HepG2 cells, Marein improves high glucose–induced insulin resistance by enhancing glucose uptake via the CaMKK/AMPK/GLUT1 pathway, promoting glycogen synthesis through the IRS/Akt/GSK-3β pathway, and suppressing gluconeogenesis via the Akt/FoxO1 axis. Additionally, Marein possesses antioxidative, antihypertensive, antihyperlipidemic, and antidiabetic properties, making it a promising candidate for metabolic and neurodegenerative disease research.

Crebinostat is a potent, broad-spectrum histone deacetylase (HDAC) inhibitor with IC₅₀ values of 0.7 nM (HDAC1), 1.0 nM (HDAC2), 2.0 nM (HDAC3), and 9.3 nM (HDAC6). It effectively induces acetylation of histone H3 and H4, and enhances the expression of Egr1, a cAMP response element-binding protein (CREB) target gene. In cultured neurons, Crebinostat increases the density of synapsin-1 puncta along dendrites, indicating enhanced synaptic connectivity. By modulating chromatin-mediated neuroplasticity, Crebinostat has been shown to improve memory performance in mice, supporting its potential for neuropsychiatric and cognitive disorder research.

Bakkenolide A is a natural sesquiterpene lactone isolated from *Petasites tricholobus*. It exhibits anti-leukemic activity by modulating epigenetic and signaling pathways, specifically through inhibition of histone deacetylase 3 (HDAC3) and regulation of the PI3K/Akt signaling cascade. These combined effects contribute to its potential as a therapeutic agent in leukemia research.

NCC-149 is a selective inhibitor of histone deacetylase 8 (HDAC8), making it a valuable tool for studying HDAC8-specific functions. It has shown utility in promoting neural differentiation, and is particularly useful in research focused on neurodevelopmental processes and potential therapeutic strategies for neurological disorders involving epigenetic dysregulation.

CM-1758 is a histone deacetylase (HDAC) inhibitor with demonstrated antitumor activity in vivo. In acute myeloid leukemia (AML) cells, CM-1758 induces the acetylation of non-histone proteins, suggesting a broader epigenetic and post-translational regulatory effect beyond chromatin remodeling. Its dual impact on tumor growth and protein acetylation supports its potential as a therapeutic agent in hematologic malignancies.

MPT0G211 is a highly potent, orally bioavailable, and selective histone deacetylase 6 (HDAC6) inhibitor, with an IC₅₀ of 0.291 nM and over 1000-fold selectivity against other HDAC isoforms. It efficiently crosses the blood–brain barrier and demonstrates neuroprotective effects by reducing tau phosphorylation and improving cognitive function in Alzheimer's disease models. Additionally, MPT0G211 exhibits anti-metastatic and anticancer activities, making it a promising therapeutic candidate for both neurodegenerative disorders and oncology research.

MPT0B390 is a potent arylsulfonamide-based histone deacetylase (HDAC) inhibitor that also functions as an inducer of tissue inhibitor of metalloproteinases 3 (TIMP3). It exhibits strong antitumor properties, including inhibition of tumor growth, metastasis, and angiogenesis. MPT0B390 shows significant antiproliferative activity against the human colon cancer cell line HCT116, with a GI₅₀ of 0.03 μM, highlighting its potential as a promising candidate for cancer therapy.

Triacetin (Glyceryl triacetate) is an orally active synthetic triester of glycerol and acetic acid that serves as a bioavailable source of acetate. It freely crosses the blood–brain barrier and cellular membranes, making it particularly effective in targeting central nervous system malignancies. In glioma cells, Triacetin increases intracellular acetate levels, promotes histone acetylation, and induces cell cycle arrest and apoptosis. Additionally, Triacetin enhances the chemotherapeutic efficacy of Temozolomide (TMZ), supporting its potential as an adjuvant in glioma treatment strategies.

NT160 is a highly potent inhibitor of class IIa histone deacetylases (HDACs), with an IC₅₀ value of 0.046 μM. Due to its strong inhibitory activity and potential central nervous system (CNS) penetration, NT160 is a valuable compound for investigating the role of class IIa HDACs in CNS-related disorders, including neurodegenerative and neuropsychiatric diseases.

RSC133 is a dual epigenetic modulator that inhibits both histone deacetylases (HDACs) and DNA methyltransferases (DNMTs). It effectively enhances the reprogramming of human somatic cells into induced pluripotent stem cells (iPSCs) and supports the maintenance of pluripotency by promoting an undifferentiated state. RSC133 is a valuable tool for stem cell research and epigenetic reprogramming studies.

Alteminostat (CKD-581) is a potent, broad-spectrum histone deacetylase (HDAC) inhibitor that targets both class I and class II HDAC isoforms. It promotes histone H3 and α-tubulin acetylation, indicating effective inhibition of nuclear and cytoplasmic HDAC activity. Alteminostat is being investigated for its therapeutic potential in hematologic malignancies, including lymphoma and multiple myeloma, and serves as a valuable tool in epigenetic cancer research.

CG347B is a selective inhibitor of histone deacetylase 6 (HDAC6) and also serves as a structural scaffold in the synthesis of other metalloenzyme inhibitors. Due to its HDAC6 selectivity, CG347B is a valuable tool for research in oncology, immunology, and neurology, where HDAC6 plays key roles in regulating protein homeostasis, immune response, and neurodegenerative processes.

MC1742 is a potent pan-HDAC inhibitor with broad activity across multiple HDAC isoforms, exhibiting IC₅₀ values of 0.1 μM (HDAC1), 0.11 μM (HDAC2), 0.02 μM (HDAC3), 0.007 μM (HDAC6), 0.61 μM (HDAC8), 0.04 μM (HDAC10), and 0.1 μM (HDAC11). It effectively increases acetylation of histone H3 and α-tubulin, markers of HDAC inhibition. MC1742 inhibits the growth of cancer stem cells (CSCs), and induces growth arrest, apoptosis, and differentiation, particularly in sarcoma CSC models, making it a promising candidate for targeting therapy-resistant cancer cell populations.

SB-429201 is a potent and selective inhibitor of histone deacetylase 1 (HDAC1), with an IC₅₀ of approximately 1.5 μM. It exhibits at least a 20-fold selectivity for HDAC1 over other class I isoforms, including HDAC3 and HDAC8. SB-429201 serves as a valuable tool for studying HDAC1-specific functions and may have potential applications in epigenetic and cancer research.

Oleuropein Aglycone (3,4-DHPEA-EA) is a bioactive polyphenol and the aglycone form of oleuropein, generated through enzymatic, acidic, or acetylated hydrolysis. It exhibits a broad range of pharmacological effects. In a TgCRND8 transgenic mouse model of Alzheimer’s disease, dietary supplementation (50 mg/kg) increases neuronal autophagic vesicles, reverses cognitive deficits, and reduces histone deacetylase 2 (HDAC2) levels in the cortex and hippocampus. In a high-fat diet-induced obesity rat model, Oleuropein Aglycone elevates urinary norepinephrine, interscapular brown adipose tissue epinephrine, and UCP1 protein levels, while reducing plasma leptin levels and total abdominal fat mass. Additionally, in a carrageenan-induced pleurisy mouse model, it mitigates lung neutrophil infiltration, lipid peroxidation, and IL-1β production. These findings highlight its potential in neurodegenerative, metabolic, and inflammatory disease research.

BRD2492 (compound 6d) is a potent and selective inhibitor of histone deacetylases HDAC1 and HDAC2, with IC₅₀ values of 13.2 nM and 77.2 nM, respectively. It exhibits over 100-fold selectivity for HDAC1/2 compared to HDAC3 and HDAC6. BRD2492 effectively inhibits the proliferation of breast cancer cell lines, with IC₅₀ values of 1.01 μM for T-47D cells and 11.13 μM for MCF-7 cells, highlighting its potential as a targeted epigenetic therapeutic in breast cancer research.

1-Naphthohydroxamic acid (Compound 2) is a potent and selective inhibitor of histone deacetylase 8 (HDAC8), with an IC₅₀ of 14 μM. It demonstrates high selectivity for HDAC8 over other HDAC isoforms, showing minimal activity against class I HDAC1 and class II HDAC6 (IC₅₀ > 100 μM). Unlike broad-spectrum HDAC inhibitors, 1-Naphthohydroxamic acid does not increase global histone H4 acetylation or reduce total intracellular HDAC activity, but it effectively induces tubulin acetylation. This selective profile makes it a valuable tool for studying HDAC8-specific functions.

YSR734 (Compound 21) is a covalent histone deacetylase (HDAC) inhibitor with IC₅₀ values of 110 nM, 154 nM, and 143 nM for HDAC1, HDAC2, and HDAC3, respectively. It induces apoptosis in leukemia cells and promotes myoblast differentiation, making it a valuable compound for both cancer research and studies related to muscle regeneration. YSR734 is particularly relevant in the investigation of therapeutic strategies for Duchenne muscular dystrophy.

PB131 is a highly selective and brain-permeable histone deacetylase 6 (HDAC6) inhibitor, exhibiting strong binding affinity with an IC₅₀ of 1.8 nM. It possesses potent anti-inflammatory activity and is particularly suited for research in inflammation-related disorders, including neuroinflammation, due to its effective central nervous system penetration and HDAC6 specificity.

MI-192 is a selective inhibitor of histone deacetylases HDAC2 and HDAC3, with IC₅₀ values of 30 nM and 16 nM, respectively. It demonstrates high selectivity for HDAC2/3 over other HDAC isoforms. MI-192 induces apoptosis in myeloid leukemia cells and exhibits both anticancer and neuroprotective activities, making it a valuable compound for research in oncology and neurodegenerative diseases.

Pivanex (AN-9) is an orally active histone deacetylase (HDAC) inhibitor derived from butyric acid. It downregulates BCR-ABL protein expression and promotes apoptosis, contributing to its antitumor effects. In addition, Pivanex exhibits antimetastatic and antiangiogenic properties, making it a promising candidate for research in hematologic malignancies and solid tumors.

BRD4884 is a potent histone deacetylase (HDAC) inhibitor that selectively targets class I HDACs. It exhibits IC₅₀ values of 29 nM for HDAC1, 62 nM for HDAC2, and 1.09 µM for HDAC3. Its differential potency across HDAC isoforms makes BRD4884 a valuable tool for investigating HDAC1/2-mediated epigenetic regulation and their roles in disease pathogenesis.

FNDR-20123 is a first-in-class, orally active histone deacetylase (HDAC) inhibitor developed for antimalarial therapy. It demonstrates potent inhibitory activity against both Plasmodium and human HDACs, with IC₅₀ values of 31 nM and 3 nM, respectively. FNDR-20123 effectively targets multiple stages of *Plasmodium falciparum*, with IC₅₀ values of 41 nM for the asexual blood stage and 190 nM for male gametocytes. It inhibits HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 with IC₅₀ values of 25, 29, 2, 11, and 282 nM, respectively, and also exhibits nanomolar-level inhibition of Class III HDAC isoforms. FNDR-20123 shows a favorable safety profile, supporting its potential as a novel antimalarial agent targeting epigenetic regulation.

Pomiferin (NSC 5113) is a natural compound that functions as a dual inhibitor of histone deacetylases (HDACs) and the mammalian target of rapamycin (mTOR). It exhibits an IC₅₀ of 1.05 μM for HDAC inhibition and an IC₅₀ of 6.2 μM for mTOR. With its dual-targeting activity, Pomiferin holds potential for anticancer research, particularly in pathways involving epigenetic regulation and cell growth signaling.

m-Carboxycinnamic acid bishydroxamide is a potent histone deacetylase (HDAC) inhibitor, demonstrating in vitro ID₅₀ values of 10 nM for HDAC1 and 70 nM for HDAC3. It effectively induces apoptosis and suppresses tumor growth, making it a promising candidate for epigenetic cancer therapy and research focused on HDAC1/3-regulated pathways.