HDAC6 Inhibitor

HDAC-IN-71 (Compound 17q) is a potent HDAC inhibitor with IC₅₀ values of 12.6, 14.1, 20, 3, and 72 nM for HDAC1, HDAC2, HDAC3, HDAC6, and HDAC10, respectively. HDAC-IN-71 induces apoptosis and can be used in cancer research.

AAK1/HDACs-IN-1 (Compound 12) is the dual inhibitor for AAK1 and HDAC, that inhibits AAK1, HDAC1, and HDAC6 with IC₅₀s of 15.9, 148.6, and 5.2 nM, respectively. AAK1/HDACs-IN-1 inhibits SARS-CoV-2 infection, suppresses the endocytosis of ACE2-SARS-CoV-2 complex, as well as AP2M1-ACE2 interaction.

C1A is a class I/II HDACs and sirtuin inhibitor with an IC₅₀ of 479 nM for HDAC6. C1A induces sustained acetylation of HDAC6 substrates, α-tubulin and HSP90. C1A shows srtong anticancer effcts, and induces apoptosis in cancer cells.

HDAC6-IN-31 (compound 8m) is a selective HDAC6 inhibitor, with the IC₅₀ value of 0.026 μM, that significantly inhibits the production and release of pro-inflammatory cytokines. While HDAC6 is critically involved in the activation of inflammasomes, HDAC6-IN-31 has the potential to inhibit NLRP3 inflammasome-driven inflammatory diseases. HDAC6-IN-31 also inhibits glioblastoma cell migration.

ALK/HDAC-IN-1 is a dual inhibitor for ALK and HDAC6, with IC₅₀s of 16 nM and 1.03 μM, respectively. ALK/HDAC-IN-1 exhibits antitumor activity.

HDAC-IN-42 (compound 14f) is a potent and selective HDAC inhibitor with IC₅₀ values of 0.19 and 4.98 µM for HDAC1 and HDAC6, respectively. HDAC-IN-42 shows anticancer and anti-proliferative activity. HDAC-IN-42 induces apoptosis and cell cycle arrest at G2/M phase.

HDAC-IN-9 is a potent and selective tubulin and HDAC dual inhibitor. HDAC-IN-9 inhibits the invasion and migration of A549 cells. HDAC-IN-9 shows potent antitumor and antiangiogenic effect in vitro and in vivo.

HDAC6-IN-87 is a selective HDAC6 inhibitor (IC₅₀ = 4.29 nM). HDAC6-IN-87 weakly inhibits HDAC1 (IC₅₀ = 749.59 nM), HDAC3 (IC₅₀ = 813.09 nM), and HDAC10 (IC₅₀ = 679.25 nM). HDAC6-IN-87 exhibits broad-spectrum antitumor activity, elevates α-tubulin acetylation levels without affecting histone H3 acetylation, and induces cell cycle arrest and apoptosis. HDAC6-IN-87 can be used for cancer-related research.

(±)-trans-BAS-2 is a hHDAC6 inhibitor with an IC₅₀ value of 0.462 μM. (±)-trans-BAS-2 serves as a scaffold for the design of proteolysis-targeting chimeras (PROTACs) and induces proteasome-dependent degradation of hHDAC6 in cells. (±)-trans-BAS-2 can be used in the research of triple-negative breast cancer and multiple myeloma.

Top/HDAC-IN-2 (45b), a Top and HDAC dual inhibitor, exhibits potent antitumor activities and induces apoptosis.

Fibrostat (Compound 5n) is a selective HDAC6 inhibitor that exerts antifibrotic effects by inhibiting HDAC6 activity, with an IC₅₀ value of 63 nM. It also exhibits good selectivity over HDAC1, HDAC3, HDAC5, HDAC8, HDAC10, and HDAC11. Fibrostat significantly downregulates fibrotic markers (fibronectin and collagen 1) in fibroblasts. Additionally, Fibrostat demonstrated no toxicity in rat-perfused heart and zebrafish larvae models. Fibrostat shows potential for research into fibrosis-related diseases.

COX-2/HDAC6-IN-1 (Compound 11e) is a dual COX-2 and HDAC6 inhibitor, with an IC₅₀ of 0.12 μM against HDAC6 and an IC₅₀ of 0.66 μM against COX-2. COX-2/HDAC6-IN-1 enhances the acetylation level of α-tubulin, regulates epigenetic gene expression, and inhibits the expression of pro-inflammatory mediators (COX-2, IL-1β, IL-6 and TNF-α). COX-2/HDAC6-IN-1 promotes Amyloid-β clearance and reduces excessive phosphorylation of Tau protein. COX-2/HDAC6-IN-1 maintains neuronal morphology by stabilizing MAP2, protects synaptic integrity by regulating synapsin, and restores the expression of memory-related genes. COX-2/HDAC6-IN-1 possesses neuroprotective activity and improves learning and memory abilities in Scopolamine (HY-N0296)-induced Alzheimer's disease mouse models. COX-2/HDAC6-IN-1 is applicable to research related to Alzheimer's disease.

HDAC6-IN-45 (Compound 15) is a selective inhibitor for HDAC6 with IC₅₀ of 15.2 nM. HDAC6-IN-45 exhibits neurotrophic through the upregulation of GAP43 and Beta-3 tubulin markers. HDAC6-IN-45 activates the Nrf2 signaling pathway, reduces H₂O₂-induced ROS production, inhibits apoptosis in PC12, and exhibits neuroprotective efficacy in SCOP-induced zebrafish Alzheimer's Disease models. HDAC6-IN-45 exhibits antioxidant activity and good blood-brain barrier (BBB) permeability.

PD-L1/HDAC6-IN-1 TFA is an orally active dual inhibitor of PD-L1 and HDAC6, with IC₅₀ values of 26.8 nM and 78 nM, respectively. PD-L1/HDAC6-IN-1 TFA binds to human and murine PD-L1 proteins with high affinity, while it reduces STAT3 phosphorylation and downregulates PD-L1 expression by inhibiting HDAC6, thus blocking the PD-1/PD-L1 interaction. PD-L1/HDAC6-IN-1 TFA exhibits potent anti-tumor activity in a mouse melanoma model. PD-L1/HDAC6-IN-1 is suitable for research on tumor immune regulation related to melanoma.

sEH/HDAC6-IN-1 (compound M9) is a selective, orally active dual inhibitor for sEH and HDAC6, with IC₅₀s of 2 nM, 0.72 nM and 5 nM, for human sEH, murine sEH and HDAC6, respectively. sEH/HDAC6-IN-1 reveals analgesic and anti-inflammatory effects.

HDAC6-IN-38 (Compound Z-7) is an inhibitor for histone deacetylase 6 (HDAC6), with an IC₅₀ of 3.25 nM. HDAC6-IN-38 inhibits proliferation of cells MGC 803.

SH-17 is a STAT3 and HDAC inhibitor, with a K_d of 0.87 μM for STAT3, and IC₅₀ values of 115.2 nM and 9.8 nM for HDAC1 and HDAC6, respectively. SH-17 blocks intracellular ATP production and mitochondrial oxidative phosphorylation, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. SH-17 is applicable to colon cancer research.

HDAC/Top-IN-1 is an orally active and pan HDAC/Top dual inhibitor with IC₅₀s of 0.036 μM, 0.14 μM, 0.059 μM, 0.089 μM and 9.8 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8. HDAC/Top-IN-1 efficiently induces apoptosis with S cell-cycle arrest in HEL cells. HDAC/Top-IN-1 has exhibits excellent in vivo antitumor efficacy.

GV-001 is a selective and orally active HDAC6 inhibitor with an IC₅₀ of 1.18 nM against HDAC6. GV-001 selectively enhances α-tubulin acetylation, reduces sIL-6 and Collagen I levels, suppresses renal cyst growth, and upregulates PC1 expression. GV-001 can be used for the study of autosomal dominant polycystic kidney disease (ADPKD).

FLT3/HDAC-IN-3 is a dual inhibitor of FLT3 and HDAC. FLT3/HDAC-IN-3 potently inhibits FLT3 (IC₅₀ = 14 nM), HDAC1 (IC₅₀ = 27 nM), HDAC6 (IC₅₀ = 20 nM), and FLT3^D853Y (IC₅₀ = 55 nM), exhibits weak activity against HDAC8, and shows no activity against HDAC4. FLT3/HDAC-IN-3 possesses kinase selectivity, plasma stability, and stability in human liver microsomes. FLT3/HDAC-IN-3 demonstrates anti-proliferative effects in a variety of hematological malignancy cell lines. FLT3/HDAC-IN-3 shows efficacy in the Jeko-1 xenograft model without observed significant toxicity. FLT3/HDAC-IN-3 can be used in the study of hematological malignancies.