hdacs

HDACs/mTOR Inhibitor 1 is a dual HDAC and mammalian target of Rapamycin (mTOR) inhibitor for treating hematologic malignancies, with IC50 values of 0.19 nM, 1.8 nM, 1.2 nM, and >500 nM for HDAC1, HDAC6, mTOR, and PI3Kα, respectively.

Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that suppresses HDAC1 activity and induces HDAC2 degradation, exhibiting oral bioavailability. Valproic Acid activates Notch1 signalling and inhibits the proliferation of small cell lung carcinoma cells, making it applicable for research into epilepsy and bipolar disorder.

AAK1/HDACs-IN-1 (Compound 12) is a dual inhibitor targeting AAK1 and HDACs, effectively inhibiting AAK1, HDAC1, and HDAC6, with IC50 values of 15.9, 148.6, and 5.2 nM, respectively. This compound also hinders SARS-CoV-2 infection by blocking the endocytosis of the ACE2-SARS-CoV-2 complex and the AP2M1-ACE2 interaction.

PARP7/HDACs-IN-1 (compound 9l) is a dual-target inhibitor aimed at PARP7 and HDAC, exhibiting antitumor properties. It demonstrates inhibition of various PARPs and HDACs with IC50 values of 83.3 nM for PARP1, 3.1 nM for PARP7, 35 nM for HDAC1, 30.3 nM for HDAC2, 35.4 nM for HDAC3, and 6.4 nM for HDAC6.

PHD2/HDACs-IN-1 is a potent mixed inhibitor of PHD2/HDACs, acting on PHD2 (IC50: 1.15 μM), HDAC1 (IC50: 19.75 μM), HDAC2 (IC50: 26.60 μM), and HDAC16 (IC50: 15.98 μM). HDACs-IN-1 is a low toxicity nephroprotective agent suitable for studies of cisplatin-induced acute kidney injury (AKI).

HDACs/EZH2-IN-1 (Compound 22a) is a dual inhibitor of HDACs and EZH2, exhibiting potent inhibitory activity, with EZH2 Y641N being suppressed by 98% at 50 nM. It selectively targets HDAC1 and HDAC6, with IC50 values of 0.23 μM and 0.07 μM, respectively. HDACs/EZH2-IN-1 effectively inhibits the proliferation of diffuse large B-cell lymphoma cells harboring EZH2 mutations and various acute myeloid leukemia cells. Additionally, this compound has the capability to induce cellular differentiation and apoptosis (Apoptosis).

HDAC/HSP90-IN-3 is a selective and potent dual inhibitor of fungal Hsp90 (IC50: 0.83 μM) and HDAC (IC50: 0.91 μM), exhibiting antifungal effects against azole-resistant Candida albicans. HDAC/HSP90-IN-3 exhibits inhibitory effects on important virulence factors and is able to downregulate the resistance genes ERG11 and CDR1.

Sodium butanoate (Sodium Butyrate) is the sodium salt of butyrate with potential antineoplastic activity. Butyrate, a short chain fatty acid, competitively binds to the zinc sites of class I and II histone deacetylases (HDACs).

Sodium 4-phenylbutyrate (TriButyrate), a transcriptional regulator, reversibly inhibits class I and II histone deacetylases (HDACs )resulting in a global increase in gene expression, decreased cellular proliferation, increased cell differentiation, and the induction of apoptosis in susceptible tumor cell populations.

Parthenolide ((-)-Parthenolide) is a natural sesquiterpene lactone that is an NF-κB inhibitor and also specifically inhibits HDAC1 protein, but is inactive against other class I/II HDACs. Parthenolide has anti-inflammatory, anti-tumor, and anti-viral activities.

2-hexyl-4-Pentynoic Acid, a valproic acid (VPA) derivatives, is a potent and robust HDACs inhibitor with IC50 value of 13 μM.

UF010 is a potent and selective HADC inhibitor with IC50 ~0.06 μM, 0.1 μM, 0.5 μM and 1.5 μM for HDACs 3, 2, 1 and 8, respectively.

Droxinostat (NS 41080) is a selective HDAC inhibitor, primarily targeting HDACs 6 and 8 with IC50 values of 2.47 μM and 1.46 μM, respectively. It is over 8-fold more selective against HDAC3 and shows no inhibition for HDAC1, 2, 4, 5, 7, 9, and 10.

PCI-24781 (Abexinostat (PCI24781)) is a new pan-HDAC inhibitor mainly targeting HDAC1 (Ki: 7 nM), also have moderate inhibitory for HDACs 2, 3, 6, and 10 and greater than 40-fold selectivity against HDAC8. Phase 1/2.

RGFP966 is an HDAC3 inhibitor (IC50: 0.08 μM) and does not affect other HDACs at concentrations up to 15 µM.

Nexturastat A is an effective and specific HDAC6 inhibitor (IC50: 5 nM). Its selectivity is >190-fold than other HDACs.

Pracinostat (SB939) is a novel HDAC inhibitor with improved in vivo properties compared to other HDAC inhibitors currently in Clinicalal trials, allowing oral dosing. Data demonstrate that Pracinostat is a potent and effective anti-tumor drug with potential as an oral therapy for a variety of human hematological and solid tumors.

Ac-Lys-AMC (Hexanamide) is a fluorescent substrate for histone deacetylase HDACs.

LSD1/HDAC-IN-2 (Compound 20c) acts as an inhibitor targeting both LSD1 and several HDACs, specifically HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with IC50 values of 39.0, 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively. This compound effectively inhibits the proliferation of cancer cells, notably colorectal cancer cells. LSD1/HDAC-IN-2 induces cell cycle arrest at the G2/M phase, inhibits cell migration, and triggers apoptosis in HCT-116 and HT-29 cells. Additionally, it demonstrates antitumor activity in mouse models without causing significant toxicity at a dose of 20 mg/kg.

Martinostat is an HDAC inhibitor that can be radiolabeled for quantitative imaging of HDACs within the central nervous system and major peripheral organs.

FF2039 (compound 1j) is a PROTAC degrader specifically targeting HDAC1, HDAC6, and various subtypes of class I, IIa, and IIb HDACs. It induces cell cycle arrest and apoptosis, showing significant antiproliferative activity against both hematological and solid tumor cell lines. The IC50 values for FF2039 against HDAC1, HDAC2, HDAC4, and HDAC6 are 1.03, 2.15, 12.4, and 0.053 μM, respectively. FF2039 exhibits antiproliferative effects on solid tumors such as MM.1S, MDA-MB-231, and U-87MG, with EC50 values of 2.8, 28, and 30 μM, respectively.

HDAC-IN-68 (Compound 29) is a potent HDAC inhibitor that disrupts microtubule structures and suppresses tumor growth. This compound notably inhibits class I HDACs, specifically HDAC1, HDAC2, and HDAC3, with IC50 values of 5.1, 11.5, and 8.8 nM, respectively.

HDAC-IN-68 (hydrochloride) (Compound 29) is an HDACs inhibitor with an IC50 value of 0.04 μM and induces microtubule fragmentation by activating katanin, a microtubule-severing protein. It is applicable in cancer research.

GSK-3β/HDAC-IN-1 (Compd 4) is a pioneering non-ATP competitive inhibitor that can penetrate the blood-brain barrier, targeting glycogen synthase kinase 3β/histone deacetylases (GSK-3β/HDACs). It exhibits IC50 values of 0.142 μM for GSK-3β, 0.03 μM for HDAC2, and 0.045 μM for HDAC6. GSK-3β/HDAC-IN-1 is utilized in Alzheimer's research.