HDAC8 Inhibitor

HDAC6-IN-51 (Compound 7e) is a selective HDAC6 inhibitor with an IC₅₀ value of 42.9 nM. HDAC6-IN-51 exhibits good anti-lung fibrosis activity.

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.

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.

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.

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 .

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.

HDAC8/PIM1-IN-1 is a synthetic multi-target-directed ligand (MTDL) derived from 2-ureido-6-nitrobenzamide, and computational simulations predict it to be a dual-target inhibitor of HDAC8 and PIM1. HDAC8/PIM1-IN-1 holds potential for applications in research related to cancer and neurodegenerative diseases.

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.

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.

HDAC8-IN-10 (compound 15) is a potent inhibitor of HDAC8, with the IC₅₀ of 7.6 nM. HDAC8-IN-10 is a HDAC8 target protein ligand that can be used to synthesize PROTAC YX862 (HY-163845).

HDAC-IN-57 is an orally active inhibitor of histone deacetylases (HDAC), with IC₅₀s of 2.07 nM, 4.71 nM, 2.4 nM and 107 nM for HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-57 can inhibits LSD1, with IC₅₀ of 1.34 μΜ. HDAC-IN-57 induces apoptosis, and has anti-tumor activity.

HDAC-IN-98 is a HDAC1, HDAC2, HDAC3 inhibitor (one of the most selective class I HDAC inhibitors) with human IC₅₀ values of 41.2 nM, 52.5 nM, and 74.3 nM respectively. HDAC-IN-98 induces H3K9 acetylation, p21 upregulation, G2/M arrest, cell apoptosis, has strong antiproliferative effects in colorectal cancer cells, low toxicity in healthy colon epithelium, modulates short-term in vitro effects via autophagy, and shows strong antitumor efficacy in vivo in the chorioallantoic membrane model (CAM) assay. HDAC-IN-98 can be used for the research of colorectal cancer.

PIM-1/HDAC-IN-2 is a robust PIM/HDAC inhibitor (IC₅₀ = 0.11 μM in MV4-11cells), which exerts a synergistic antiproliferative effect through a dual mechanism of inhibiting PIM1 kinase and selectively inhibiting HDAC6. PIM-1/HDAC-IN-2 induces cell apoptosis. PIM-1/HDAC-IN-2 remarkably induces the cleavage of PARP, thereby initiating the arrest of the cell cycle in G1 phase and a reduction in S phase. PIM-1/HDAC-IN-2 demonstrates significant anticancer efficacyin the MV4-11 xenograft model without notable toxicity^[1]_.

NN-390 is a potent and selective HDAC6 inhibitor, with an IC₅₀ of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma).

HDAC-IN-104 is a potent and selective class I Histone deacetylases (HDAC) inhibitor with an IC₅₀ of 25 nM. HDAC-IN-104 exerts potent antiproliferative and antitumor effects by inhibiting glycolysis and OXPHOS via blockade of the PI3K/AKT signaling pathway, and these effects are synergistically enhanced when combined with the FMS-like tyrosine kinase 3 (FLT3) inhibitor Quizartinib (AC220) (HY-13001). HDAC-IN-104 induces significant early and late apoptosis. HDAC-IN-104 can be used for acute myeloid leukemia (AML) research.

G4/HDAC-IN-1 (compound a6) is a G4/HDAC dual-targeting compound. G4/HDAC-IN-1 inhibits intracellular HDAC activity with an IC₅₀ value of 1.1 μM, and induces G4 formation. G4/HDAC-IN-1 inhibits TNBC proliferation and tumor growth in TNBC xenograft model. G4/HDAC-IN-1 can be used for the research of cancer.

HDAC8-IN-17 is a histone deacetylase 8 inhibitor with human IC₅₀ values of 0.08 μM, 0.44 μM, and 1.9 μM, and high selectivity over HDAC1, HDAC2, HDAC3, and HDAC6. HDAC8-IN-17 exhibits slow-binding, reversible uncompetitive inhibition via allosteric binding to the enzyme-substrate complex. HDAC8-IN-17 induces selective hyperacetylation of SMC3. HDAC8-IN-17 can be used for the research of cancer.

HDAC6/HSP90-IN-1 (compound 17) is a potent and selective dual inhibitor of HDAC6 and HSP90, with IC₅₀ values of 4.3 and 46.8 nM, respectively. HDAC6/HSP90-IN-1 down-regulates PD-L1 expression in INF-γ treated H1975 lung cancer cells. HDAC6/HSP90-IN-1 inhibits tumor growth in human H1975 xenograft mice.