NF-κB/IκB

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.

HPB is a selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 31 nM. It demonstrates over 30-fold selectivity for HDAC6 compared to HDAC1, making it a valuable tool for studying HDAC6-specific biological functions and a promising candidate for the development of targeted therapies in diseases involving HDAC6 dysregulation.

SelSA is a selective and orally active histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 56.9 nM. It also inhibits ERK1/2 phosphorylation, contributing to its anticancer effects. SelSA suppresses the proliferation of breast cancer and hepatocellular carcinoma cells with IC₅₀ values ranging from 0.58 to 2.6 μM, inhibits migration and invasion of Huh7 cells, and induces apoptosis. In vivo, SelSA demonstrates significant antitumor activity, supporting its potential as a therapeutic agent for solid tumors.

KH16 is a potent histone deacetylase (HDAC) inhibitor with low nanomolar activity, selectively targeting class I HDACs—HDAC1, HDAC2, and HDAC3—with IC₅₀ values ranging from 6 to 34 nM. It effectively induces apoptosis and exhibits broad-spectrum antitumor activity across cancer cells with diverse gene expression profiles, making it a promising candidate for epigenetic cancer therapy research.

Licochalcone D is a naturally occurring flavonoid primarily found in the root of *Glycyrrhiza uralensis* (Chinese licorice). It functions as a potent and orally active inhibitor of the NF-κB p65 subunit, a key regulator of inflammation and cancer-related signaling pathways. Licochalcone D exhibits broad pharmacological properties, including antioxidant, anti-inflammatory, and anticancer activities, making it a promising candidate for research in inflammation-related diseases and oncology.

PB94 is a selective inhibitor of histone deacetylase 11 (HDAC11), with an IC₅₀ of 108 nM. It can be radiolabeled as [¹¹C]-PB94 for positron emission tomography (PET) imaging, enabling in vivo assessment of brain uptake and metabolic properties. PB94 has demonstrated efficacy in alleviating neuropathic pain in mouse models and holds potential as a research tool for investigating HDAC11-related mechanisms in neurological disorders.

AES-350 is a potent and orally bioavailable histone deacetylase 6 (HDAC6) inhibitor, with an IC₅₀ of 0.0244 μM and a Kᵢ of 0.035 μM. It also exhibits inhibitory activity against HDAC3 and HDAC8, with IC₅₀ values of 0.187 μM and 0.245 μM, respectively. AES-350 induces apoptosis in acute myeloid leukemia (AML) cells through HDAC inhibition, making it a promising compound for AML research and the development of epigenetic-based cancer therapies.

ITF 3756 is a potent and selective inhibitor of histone deacetylase 6 (HDAC6). In vitro, it effectively reduces the expression of PD-L1 on human monocytes and CD8⁺ T cells, suggesting immunomodulatory potential. ITF 3756 also exhibits antitumor activity, making it a promising candidate for cancer immunotherapy and epigenetic modulation research.

HL23 is a histone deacetylase (HDAC) inhibitor with demonstrated efficacy against hepatocellular carcinoma (HCC). It enhances acetylation at the TXNIP promoter, leading to upregulation of TXNIP expression and modulation of potassium channel activity, ultimately inducing TXNIP-dependent potassium deprivation. HL23 effectively suppresses HCC progression and metastasis, and exhibits a synergistic antitumor effect when combined with Sorafenib, outperforming the combination of Sorafenib and Vorinostat in preclinical models.

GEM144 is a potent and orally bioavailable dual inhibitor of DNA polymerase α (POLA1) and histone deacetylase 11 (HDAC11). It promotes p53 acetylation, induces p21 activation, and triggers G1/S cell cycle arrest followed by apoptosis. GEM144 exhibits significant antitumor efficacy in human orthotopic malignant pleural mesothelioma xenograft models, highlighting its potential as a targeted therapeutic agent for aggressive thoracic malignancies.

F-SAHA is a histone deacetylase inhibitor (HDACi) structurally derived from suberoylanilide hydroxamic acid (SAHA). Its fluorine-18 (^18F) labeled derivative enables non-invasive imaging of HDAC expression and activity, making F-SAHA a valuable tool for tumor imaging research and the assessment of epigenetic modulation in vivo.

MIR002 is a potent, orally bioavailable dual inhibitor targeting DNA polymerase α (POLA1) and histone deacetylase 11 (HDAC11). It induces p53 acetylation, upregulates p21 expression, and triggers G1/S cell cycle arrest followed by apoptosis. MIR002 demonstrates significant antitumor efficacy in vivo, highlighting its potential as a therapeutic agent for cancers driven by POLA1 and HDAC11 dysregulation.

KPZ560 is a potent inhibitor of histone deacetylases HDAC1 and HDAC2, with IC₅₀ values of 12 nM and 68 nM, respectively. It has been shown to enhance dendritic spine density in granule neurons of mice, indicating potential neurotrophic effects. Additionally, KPZ560 inhibits the proliferation of MCF breast cancer cells, supporting its potential application in both neurobiological and oncological research.

MPI_5a is a potent and selective inhibitor of histone deacetylase 6 (HDAC6), with an IC₅₀ of 36 nM. It exhibits minimal activity against other HDAC isoforms, demonstrating high isoform selectivity. In cellular assays, MPI_5a effectively inhibits acylated tubulin accumulation with an IC₅₀ of 210 nM, highlighting its utility in modulating HDAC6-dependent processes for potential therapeutic applications.

MOCPAC is an HDAC1 specific substrate.

QTX125 is a potent and highly selective inhibitor of histone deacetylase 6 (HDAC6), demonstrating excellent specificity over other HDAC isoforms. It exhibits significant antitumor activity through selective inhibition of HDAC6-mediated pathways. Both the salt and free base forms of QTX125 display comparable biological activity at equivalent molar concentrations, ensuring consistent pharmacological effects across different formulations.

Triciferol is a multifunctional small molecule that acts as both a vitamin D receptor (VDR) agonist and a histone deacetylase (HDAC) antagonist. It binds directly to VDR with an IC₅₀ of 87 nM and exhibits 1,25-dihydroxyvitamin D₃ (1,25D)-like potency in activating multiple VDR target genes. In addition to its transcriptional effects, Triciferol induces significant tubulin hyperacetylation and enhances histone acetylation, contributing to its antiproliferative and cytotoxic activities. This dual mechanism highlights its potential as a therapeutic agent in cancer and epigenetic modulation.

YX968 is a potent and selective PROTAC degrader targeting histone deacetylases HDAC3 and HDAC8, with DC₅₀ values of 1.7 nM and 6.8 nM, respectively. By inducing degradation of these epigenetic regulators, YX968 promotes apoptosis and exhibits significant antitumor activity, representing a promising therapeutic strategy for cancers driven by aberrant HDAC3/8 activity.

AR420626 is a selective agonist of free fatty acid receptor 3 (FFAR3, also known as GPR41), with an IC₅₀ of 117 nM. It demonstrates anti-inflammatory, antitumor, and antidiabetic activities. AR420626 improves neurogenic diarrhea by modulating neural pathways mediated by nicotinic acetylcholine receptors (nAChRs). In cancer models, it suppresses the growth of HepG2 xenografts and inhibits hepatoma cell proliferation through apoptosis induction. Additionally, AR420626 mitigates allergic asthma and eczema and enhances glucose uptake by activating FFAR3-mediated Ca²⁺ signaling, offering potential therapeutic benefits in metabolic disorders such as diabetes.

JPS016 is a benzamide-based PROTAC that recruits the Von Hippel-Lindau (VHL) E3 ligase to selectively degrade class I histone deacetylases (HDACs). It is a potent degrader of HDAC1/2, leading to broad transcriptional changes and enhanced apoptosis in HCT116 cells, supporting its application in epigenetic and cancer research.

Berkeleyacetal C is a meroterpenoid compound that acts as an anti-inflammatory agent by inhibiting the NF-κB, ERK1/2, and IRF3 signaling pathways. It effectively reduces the expression of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide production in macrophages. Additionally, Berkeleyacetal C suppresses the expression and secretion of key pro-inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1β, MIP-1α, and MCP-1, while also inhibiting neutrophil activation and reactive oxygen species (ROS) production. This compound is valuable for research into inflammatory disorders.

SMU127 is an agonist of the toll-like receptor 1/2 (TLR1/2) heterodimer, primarily targeting NF-κB signaling. It effectively induces TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs) at concentrations of 0.01 to 1 μM and exhibits an EC50 of 0.55 μM in cells expressing human TLR2. In vivo studies demonstrate that SMU127 (0.1 mg/animal) significantly reduces tumor volume in a 4T1 murine mammary carcinoma model, making it a valuable tool for research on immune response and cancer therapy.

Theophylline sodium acetate functions as a potent phosphodiesterase (PDE) inhibitor, specifically targeting PDE3 to promote the relaxation of airway smooth muscle. It also acts as an adenosine receptor antagonist and histone deacetylase (HDAC) activator, contributing to its anti-inflammatory properties by elevating IL-10 levels and inhibiting NF-κB translocation to the nucleus. Additionally, Theophylline sodium acetate is known to induce apoptosis, making it a valuable reagent for research on asthma and chronic obstructive pulmonary disease (COPD).

CAY10512 is a potent NF-κB inhibitor that effectively suppresses the upregulation of NF-κB-sensitive proinflammatory microRNAs, including miRNA-9, miRNA-125b, miRNA-146a, and miRNA-155, in cerebrospinal fluid and extracellular environments. This compound significantly reduces the release of pro-inflammatory cytokines such as TNF-α, MCP-1, IL-8, and IL-6. CAY10512 is valuable for research applications focused on neuroinflammation, islet transplantation, and the regulation of microRNA.

SMU-L11-R is a selective TLR7 agonist that demonstrates an EC50 of 0.012 μM for human TLR7. This compound specifically activates TLR7, recruits MyD88, and initiates the MAPK/NF-κB signaling pathways, resulting in the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in both mouse and human peripheral blood mononuclear cells. Additionally, SMU-L11-R promotes M1-like macrophage polarization and exhibits synergistic anti-tumor effects in combination with PD-L1 inhibitors through the upregulation of CD8+ T cells, making it a valuable tool for research in colorectal cancer.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside is a potent anti-inflammatory agent that targets key signaling pathways, including NF-κB, MAPK, and Akt. This compound significantly reduces the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-induced RAW 264.7 macrophages. Additionally, it suppresses the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, making it valuable for research into inflammation and related disorders.

Cudraflavone B is a prenylated flavonoid that functions as a dual inhibitor of COX-1 and COX-2, demonstrating significant anti-inflammatory and anti-tumor activity. This compound inhibits the translocation of nuclear factor κB (NF-κB) in macrophages, leading to decreased tumor necrosis factor α (TNFα) gene expression and secretion. Additionally, Cudraflavone B induces the mitochondrial apoptotic pathway while activating MAPK signaling pathways, including p38 and ERK, and upregulating SIRT1 expression. These mechanisms contribute to its efficacy in attenuating the growth of human oral squamous cell carcinoma cells, making it a valuable tool for cancer research.

rel-Cleroindicin F is an anti-inflammatory agent that targets the NF-κB signaling pathway. It effectively inhibits the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) by downregulating NF-κB and its kinases in LPS-stimulated RAW 264.7 cells. This mechanism contributes to the suppression of inducible nitric oxide synthase expression, leading to decreased NO production. Rel-Cleroindicin F is valuable for research into inflammatory processes and potential therapeutic applications.

sEH-IN-21 is a potent inhibitor of soluble epoxide hydrolase (sEH), displaying IC50 values of 0.1 nM for both human and mouse sEH isoforms. This compound effectively inhibits NF-κB signaling pathways and demonstrates significant anti-inflammatory activity by reducing the release of pro-inflammatory cytokines IL-6 and TNF-α. Additionally, sEH-IN-21 helps maintain intestinal barrier integrity, making it a valuable tool for research on inflammatory bowel disease (IBD) and related inflammatory conditions.

CDN-3 is a cyclic dideoxy nucleotide derivative that functions as an antitumor agent. It stimulates the production of IFN-β and activates the IRF-3 and NF-κB signaling pathways, leading to the induction of type I interferons and pro-inflammatory cytokines such as IL-6 and TNF-α. CDN-3 effectively inhibits the proliferation of cancer cells, making it a valuable tool for investigating mechanisms of colon cancer progression and therapeutic strategies.

Panaxytriol is a potent NF-κB inhibitor that effectively reduces the nuclear translocation of NF-κB. This mechanism leads to decreased production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, as well as nitric oxide in response to LPS stimulation. Additionally, Panaxytriol promotes the upregulation of CYP3A4 through activation of the nuclear receptors PXR and CAR. Its ability to improve motor dysfunction in mouse models of brain inflammation makes Panaxytriol valuable for research into neurodegenerative diseases, such as Alzheimer's disease.

Anti-inflammatory agent 41 is an effective inhibitor of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines IL-6 and TNF-α in J774A.1, THP-1, and LX-2 cells. This compound also inhibits the activation of the NF-κB signaling pathway. Its primary applications include investigating the mechanisms of inflammation and assessing potential therapeutic strategies in inflammation-related diseases.

Sabialimon P is a nitric oxide (NO) release inhibitor with an IC50 of 18.12 μM. This compound exhibits potent anti-inflammatory effects by significantly reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and the enzyme iNOS in LPS-stimulated RAW264.7 macrophage cells. Additionally, Sabialimon P inhibits the expression of COX-2 and the NF-κB/p65 pathway, making it a valuable tool for research into inflammation-related pathways and potential therapeutic applications.

Anti-inflammatory agent 20 is a potent inhibitor of nitric oxide (NO) activity, demonstrating significant anti-inflammatory properties. This compound effectively suppresses lipopolysaccharide (LPS)-induced inflammation by inhibiting the activation of NF-κB and MAPK signaling pathways, leading to a reduction in pro-inflammatory cytokines such as IL-6, TNF-α, as well as the enzymes iNOS and COX-2. It serves as a valuable tool for research applications focused on inflammation and related signaling mechanisms.

Skimmianine is an orally active furoquiniline alkaloid present mainly in the Rutaceae family. Skimmianine has analgesic, antispastic, sedative, and anti-inflammatory properties. Skimmianine inhibits acetylcholinesterase (AChE) (IC50 = 8.6 μg/mL). Skimmianine exhibits cytotoxicity against a variety of cancer cell lines and genotoxicity. Skimmianine has antioxidant and anti-inflammatory effects on ischemia-reperfusion (IR) injury. Skimmianine exerts anti-inflammatory effects through activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) pathway. Skimmianine is neuroprotective by targeting the NF-κB activation pathway to prevent neuroinflammation. Skimmianine inhibits the release of histamine, intracellular Ca2+ signaling and protein kinase C signaling.

Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a Kd value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis.

Isoginkgetin is a pre-mRNA splicing inhibitor that modulates splicing processes critical for gene expression. In addition to its primary function, Isoginkgetin inhibits the activities of the signaling proteins Akt and NF-κB, as well as matrix metalloproteinase-9 (MMP-9). This compound is known to inhibit the 20S proteasome, inducing apoptosis and activating autophagy, making it a valuable tool in cancer research and studies focused on cellular stress responses.

Oxaprozin is a potent, orally active cyclooxygenase (COX) inhibitor, demonstrating IC50 values of 2.2 μM for human platelet COX-1 and 36 μM for IL-1-stimulated human synovial cell COX-2. This compound exhibits significant anti-inflammatory activity and is known to inhibit the activation of NF-κB, promoting cell apoptosis. The inhibition of the Akt/IKK/NF-κB signaling pathway is a key mechanism underlying its anti-inflammatory properties, making Oxaprozin valuable for research in inflammation and related disorders.

Cryptanoside A is a potent Na+/K+-ATPase inhibitor derived from the stems of Cryptolepis dubia. This cardiac glycoside epoxide exhibits significant cytotoxic effects against various cancer cell lines. Additionally, Cryptanoside A enhances the expression of Akt and the p65 subunit of NF-κB, making it a valuable tool for studying cancer biology and the regulatory pathways involved in cell survival and proliferation.