HDAC6 Inhibitor

sEH/HDAC6-IN-2 is a potent dual soluble epoxide hydrolase (sEH) and HDAC6 inhibitor with IC₅₀s of 0.9 nM, 46.8 nM, and 8 nM for human sEH, mouse sEH, and HDAC6, respectively. sEH/HDAC6-IN-2 can be used for the study of inflammatory pain.

AMC-3-030 is a selective and potent dual inhibitor targeting HDAC6 and chymotrypsin-like proteasome with IC₅₀ values of 884 and 4.17 nM. AMC-3-030 has a proliferation inhibitory effect. AMC-3-030 can reduce α-tubulin and β-actin levels. AMC-3-030 can be used for research of multiple myeloma.

HDAC1/6-IN-3 is a potent HDAC inhibitor. HDAC1/6-IN-3 shows excellent inhibitory activities against HDAC1 (IC₅₀ = 1.1 nM) and HDAC6 (IC₅₀ = 2.7 nM). HDAC1/6-IN-3 significantly arrests HepG2 cells at the G0/G1 phase and induces apoptosis and pyroptosis. HDAC1/6-IN-3 exhibits significant antitumor activity in the HepG2 xenograft mode. HDAC1/6-IN-3 can be used for the study of cancers such as liver cancer, lung cancer, colon cancer and breast cancer.

Leuxinostat is an inhibitor for HDAC with IC₅₀ of 30 nM for hHDAC6. Leuxinostat inhibits the proliferation of cells THP1, K562, U937 and MEK1, induces apoptosis in leukemia cells NB4 and MOLT-4. Leuxinostat inhibits the expansion of hematopoietic stem cells and exhibits antileukemic activity in zebrafish models.

Nanatinostat (CHR-3996) TFA is a potent, class I selective and orally active HDAC inhibitor with IC₅₀s of 3 nM, 4 nM, and 7 nM for HDAC1, HDAC2, and HDAC3, respectively. Nanatinostat TFA has low activity against HDAC5 (IC₅₀ of 200 nM) and HDAC6 (IC₅₀ of 2100 nM). Nanatinostat TFA induces apoptosis in myeloma cells. Nanatinostat TFA has potent anticancer effects, such as myeloma, advanced solid tumours and colorectal cancer.

CM-414 is a brain-penetrant phosphodiesterase 5 (PDE5) and HDAC inhibitor with IC50s of 60 nM, 91 nM, 310 nM, 322 nM and 490 nM for PDE5, HDAC6, HDAC1, HDAC3 and HDAC2, respectively. CM-414 diminishes brain Aβ and tau phosphorylation (pTau) level in Tg2576 mice. CM-414 can be used for the study of Alzheimer's disease (AD).

MC2625 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2625 show selective HDAC3 and HDAC6 inhibition with IC₅₀s of 80 nM and 11 nM. MC2625 increases acetyl-H3 and acetyl-tubulin levels and inhibits cancer stem cells (CSCs) growth by apoptosis induction.

IOR-160 is a dual inhibitor of casein kinase 2 (CK2) and HDACs. IOR-160 exhibits high selectivity for CK2 (IC₅₀ = 1.7 nM) and broad inhibitory activity against HDAC (HDAC 1, 2, 3, and 6 with IC₅₀s of 3.3 nM, 24.0 nM, 3.9 nM, and 13.0 nM, respectively, with low activity for HDAC8). IOR-160 modulates key cellular signaling pathways by inhibiting AKT phosphorylation and increasing acetylated α-tubulin. IOR-160 inhibits tumor growth and reduces tumor burden through dual CK2/HDAC inhibition. IOR-160 is indicated for use in triple-negative breast cancer research.

HDAC6-IN-69 is a brain-penetrant and highly selective HDAC6 inhibitor with an IC₅₀ of 4.0 nM. HDAC6-IN-69 shows >176-fold against other HDAC isoforms. HDAC6-IN-69 engages the target in neuronal cells by dose-dependently upregulating acetylated α-tubulin in virto. HDAC6-IN-69 has neuroprotective effect and can be used for ischemic stroke research .

AC-340 is a potent hybrid VDR agonist/HDAC inhibitor. AC-340 superinduces VDR target genes (e.g., CYP24A1) and inhibits HDAC6 (IC₅₀ = 0.37 μM) with ~10-fold selectivity over HDAC2. AC-340 induces VDR hyperagonism by causing widespread protein hyperacetylation (e.g., tubulin and H3K9/K27), which leads to elevated H3K27 acetylation on VDR target genes. AC-340 can be used for melanoma cancer research.

NL-103 is an inhibitor of histone deacetylases (HDACs) and Hedgehog, with the IC₅₀ values ​​of 21.3 nM, 57 nM, 74 nM, and 680 nM for HDAC1, HDAC2, HDAC3, and HDAC6, respectively. NL-103 can downregulate the expression of Gli2. NL-103 can be used in anti-cancer research.

A2AAR/HDAC-IN-1 (compound 14c) is an orally active, potent and balanced A_2AAR/HDAC dual inhibitor, with a K_i of 163.5 nM for A_2AAR and an IC₅₀ of 145.3 nM for HDAC1. A2AAR/HDAC-IN-1 shows anticancer activity.

HDAC6-IN-41 (Compound E24) is a selective inhibitor for histone deacetylase 6 (HDAC6), with IC₅₀ of 14 and 422 nM, for HDAC6 and HDAC8, respectively. HDAC6-IN-41 upregulates the acetylation of α-tubulin and histone site SMC3.

HDAC6-IN-62 (Compound 2.12) is a selective HDAC6 inhibitor, with an IC₅₀ value of 0.25 nM. HDAC6-IN-62 can be used in the research of Charcot-Marie-Tooth disease.

Rodin-C is a selective HDAC inhibitor with IC₅₀s of 0.059, 0.18   and 5.39 μM for HDAC1, HDAC2 and HDAC11, respectively, over HDAC3-10. Rodin-C significantly inhibits the HDAC-CoREST complex with low hematological toxicity. Rodin-C can be used for neurologic disorders such as Alzheimer’s disease research.

HDAC6-IN-82 is a selective HDAC6 inhibitor with an IC₅₀ of 4.9 nM against HDAC6. HDAC6-IN-82 inhibits HDAC1 (112 nM), HDAC2 (737 nM), HDAC3 (623 nM), HDAC8 (1140 nM), HDAC10 (91.4 nM) and HDAC11 (219 nM). HDAC6-IN-82 reduces cancer cell viability, induces cell cycle arrest, triggers apoptosis, and increases the acetylation levels of H3K9 and α-tubulin. HDAC6-IN-82 can be used in cancer-related research such as leukemia.

HDAC-IN-46 (compound 12c) is a potent HDAC inhibitor with an IC₅₀ value of 0.21 μM and 0.021 μM for HDAC1 and HDAC6, respectively. HDAC-IN-46 upregulates p-p38, and downregulates Bcl-xL and cyclin D1 in MDA-MB-231 cells. HDAC-IN-46 induces significant G2 phase arrest and apoptosis. HDAC-IN-46 can be used for researching triple-negative breast cancer (TNBC).

GRK2 modulator 1 is an orally active, brain-penetrant and selective GRK2 modulator. GRK2 modulator 1 enhances the active, non-phosphorylated GRK2 and prevents mitochondrial GRK2 and TOMM6 aggregation. GRK2 modulator 1 enhances the non-amyloidogenic processing of APP and prevent PHF-tau, neurodegeneration, and neuronal loss. GRK2 modulator 1 decreases the senescence marker, UPAR, reduces the Alzheimer disease (AD)-related mortality, and prolongs survival. GRK2 modulator 1 exerts neuroprotection by inhibiting HDAC6, and counteracts age-related cardiac dysfunction. GRK2 modulator 1 can be used for research on AD.

HDAC6-IN-36 (compound 11d) is an inhibitor of HDAC6 with IC₅₀ value of 8.64 nM. HDAC6-IN-36 induces neurite outgrowth of PC12 cells without producing toxic effects.

HDAC6-IN-61 (Compound 4e) is a HDAC6 inhibitor (IC₅₀: 73 nM) with selectivity over other HDAC isoforms. HDAC6-IN-61 is also a GPR40 activator. HDAC6-IN-61 increases acetylated tubulin and ERK phosphorylation levels. HDAC6-IN-61 can be used for research of neuroinflammation such as Alzheimer's disease.