HDAC

ACY-241 is a new, selective and orally available inhibitor of HDAC6.

CUDC-907 (Fimepinostat) is a single small molecule inhibitor that targets both PI3K and HDAC. CUDC-907 is more efficacious than either a single PI3K or HDAC inhibitor reference compound or a combination of the two single agents at maximally tolerated doses.

MC1568 is a member of HDAC inhibitors that inhibits the histone deacetylase class II by modifying the genetic expression of various important genes of cell cycle mostly at G1 phase, resulting in the death of breast cancer cells by apoptosis.

MS-275 (Entinostat) is a potent HDAC inhibitor with IC50 of 0.3 and 8uM for HDAC1 and HDAC3, respectively.

Romidepsin strongly inhibits HDAC1 and HDAC2 with IC5N/A of 1.6 nM and 3.9 nM, respectively, but is relatively weak in inhibiting HDAC4 and HDAC6 with IC5N/A 25 nM and 79N/A nM, respectively.

Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.

ACY-738 is a potent and selective HDAC6 inhibitor with improved brain bioavailability. ACY-738 inhibits HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs.

LAQ824 (NVP-LAQ824) is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma.

Trichostatin A (TSA) inhibits the HDACs 1, 3, 4, 6 and 10 with IC50 values around 20 nM.

ITF2357 (Givinostat) is a HDACs inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities.

SB939 is an oral inhibitor of HDAC, selective for class I, II and IV HDACs and displays an IC50 value of 77 nM in an in vitro HDAC1 activity assay.

CAY10603 is a potent and selective HDAC6 inhibitor with IC50 of 2 pM, >200-fold selectivity over other HDACs.

Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold).

LBH589 is a hydroxamic acid and acts as a non-selective HDAC inhibitor with IC5o of HDAC1 to be 0.23 nM.

PCI-24781 is a broad-spectrum phenyl hydroxamic acid HDAC inhibitor.

R306465 is a novel hydroxamate-based histone deacetylase (HDAC) inhibitor with broad-spectrum antitumour activity against solid and haematological malignancies in preclinical models.

MGCD0103 (Mocetinostat) is a benzamide histone deacetylase inhibitor by inhibiting mainly histone deacetylase 1 (HDAC1), but also HDAC2, HDAC3, and HDAC11.

JNJ-26481585 (Quisinostat) is a pan-HDAC inhibitor with marked potency toward HDAC1 (IC(50), 0.16 nmol/L).

Vorinostat is an inhibitor of HDACs, inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors.

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.

Belinostat (PXD101) is a HDAC inhibitor that inhibits HDAC activity in HeLa cell extracts with an IC50 of 27 nM.

RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM, exhibits > 200-fold selectivity over other HDAC.

TMP 269 is a potent, selective class IIa HDAC inhibitor with IC50 of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively.

AR-42 is a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit.

CUDC-101 is a novel compound which inhibits multiple targets, which is designed to inhibit HDAC, EGFR and Her2.

Droxinostat is a selective inhibitor of HDAC3, HDAC6, and HDAC8 that shows comparable inhibition of HDAC6 and HDAC8 with IC50 = 2.47 and 1.46 μmol/L, respectively.

Parthenolide ((-)-Parthenolide) is a sesquiterpene lactone which occurs naturally in the plant feverfew (Tanacetum parthenium).

Pyroxamide (NSC 696085) is a potent inhibitor of affinity-purified HDAC1 and causes the accumulation of acetylated core histones in MEL cells cultured with the agent.

Sodium butyrate (NaB, Butanoic acid sodium salt), sodium salt of butyric acid, is a histone deacetylase inhibitor and competitively binds to the zinc sites of class I and II histone deacetylases (HDACs).

Valproic acid sodium salt (Sodium Valproate) is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2.

Tubacin (tubulin acetylation inducer) is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM.

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.

Boc-Lys(Ac)-AMC is a cell-permeable fluorometric substrate for histone deacetylases (HDACs). When cleaved by HDAC enzymes, it releases a fluorescent signal with excitation and emission maxima at 355 nm and 460 nm, respectively. This compound is valuable for studying HDAC activity in various biological contexts and can be utilized in high-throughput screening assays to evaluate enzyme inhibitors.

VUBI1 analogue-1 is an analogue of VUBI1, functioning as a selective activator of the SOS1 pathway with a Kd of 44 nM. This compound is valuable for studying SOS1 activation mechanisms and provides a basis for the synthesis of (4S)-PROTAC SOS1 degrader-1. Its applications include investigations into targeted degradation and modulation of cellular pathways involving SOS1, offering insights into cellular signaling and potential therapeutic strategies.

HC-Toxin is a potent histone deacetylase (HDAC) inhibitor with an IC50 of 30 nM. This cyclic tetrapeptide effectively induces apoptosis in tumor cells, demonstrating significant anticancer activity. Its mechanism of action makes it valuable for research in cancer therapy and the modulation of gene expression.

Theophylline, a potent phosphodiesterase (PDE) inhibitor, primarily targets PDE3, leading to relaxation of airway smooth muscle and enhanced bronchodilation. This compound also functions as an adenosine receptor antagonist and exhibits anti-inflammatory properties by elevating IL-10 levels and inhibiting NF-κB translocation into the nucleus. Additionally, Theophylline has been shown to induce apoptosis in certain cell types. Its applications are particularly relevant in the research of asthma and chronic obstructive pulmonary disease (COPD).

HDAC3-IN-2 is a potent inhibitor of histone deacetylase 3 (HDAC3), with an IC50 value of 14 nM. This pyrazinyl hydrazide compound exhibits cytotoxicity against triple-negative breast cancer cell lines, demonstrating an IC50 of 0.55 μM for 4T1 cells and 0.74 μM for MDA-MB-231 cells. In in vivo studies using tumor-bearing mouse models, HDAC3-IN-2 effectively enhances histone acetylation levels at H3K9, H3K27, and H4K12 while promoting apoptosis through increased caspase-3, caspase-7, and cytochrome c levels, alongside a decrease in proliferation markers such as Bcl-2, CD44, EGFR, and Ki-67.

HDAC1/6-IN-3 is a potent inhibitor of histone deacetylases 1 and 6 (HDAC1 and HDAC6). It demonstrates strong inhibitory activity, with IC50 values of 1.1 nM for HDAC1 and 2.7 nM for HDAC6. This compound effectively induces cell cycle arrest in the G0/G1 phase and promotes both apoptosis and pyroptosis in HepG2 cells. Additionally, HDAC1/6-IN-3 exhibits significant antitumor effects in the HepG2 xenograft model and is valuable for research focused on various types of cancer, including liver, lung, colon, and breast cancers.

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.