HDAC6 Inhibitor

PHD2/HDACs-IN-1 is a potent PHD2/HDACs hybrid inhibitor (IC₅₀s of 1.15 μM, 19.75 μM, 26.60 μM and 15.98 μM for PHD2, HDAC1, HDAC2 and HDAC6, respectively). PHD2/HDACs-IN-1 is a low-toxicity renoprotective agent for research of cisplatin-induced acute kidney injury (AKI).

LASSBio-1911 is a potent inhibitor of HDAC6. LASSBio-1911 shows antitumor in hepatocellular carcinoma (HCC) cells with minimal on normal cells.

CYP17A1/HDAC6-IN-1 (compound 12) is a potent inhibitor of CYP17A1/HDAC6, with IC₅₀ of 0.284μM and 0.6015 μM,respectively. CYP17A1/HDAC6-IN-1 has anti-tumor activity.

HDAC8-IN-2 (compound 5o) is a potent HDAC8 inhibitor, with IC₅₀ values of 0.27 and 0.32 μM for smHDAC8 (Schistosoma mansoni histone deacetylase 8) and hHDAC8, respectively. HDAC8-IN-2 shows significant killing of the schistosome larvae. HDAC8-IN-2 markedly impairs egg laying of adult worm pairs.

FT108 is a selective HDAC6 inhibitor with an IC₅₀ of 0.026 μM. FT108 exhibits only modest in vitro activity against HDAC3 and HDAC8 with IC₅₀ values of 6.68 and 4.07 μM. FT108 increases acetylation of tubulin and has little to no effect on acetylated histone H3 levels. FT108 lacks activity against myeloproliferative neoplasm cell lines, and does not suppress JAK2 phosphorylation or its downstream targets pSTAT3 and pSTAT5.

HDAC3-IN-4 is a selective and orally active HDAC3 inhibitor with an IC₅₀ of 89 nM. HDAC3-IN-4 induces the degradation of PD-L1 by regulating cathepsin B (CTSB) in the lysosomes, with a DC₅₀ of 5.7 μM. HDAC3-IN-4 shows better selectivity for HDAC3 over HDAC1, HDAC6, HDAC7, and HDAC8.

GSK-3β/HDAC-IN-1 (Compd 4) is a brain-penetrant and first in class dual non-ATP-competitive Glycogen Synthase Kinase 3β/Histone Deacetylases (GSK-3β/HDACs) Inhibitor with IC₅₀s of 0.142, 0.03 and 0.045 μM against GSK-3β, HDAC2 and HDAC6, respectively. GSK-3β/HDAC-IN-1 can be used for Alzheimer’s disease research.

HDAC8-IN-3 (compound P19) is a potent HDAC8 inhibitor with IC₅₀ value of 9.3 μM and produces thermal stabilization. HDAC8-IN-3 has cytotoxicity and induces apoptosis in leukemic cell lines.

PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC₅₀s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC₅₀s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.

HDACs/EZH2-IN-1 (Compound 22a) is a HDACs/EZH2 inhibitor (EZH2 Y641N inhibition rate at 50 nM: 98%), with selective inhibition against HDAC1 and HDAC6 (IC₅₀: 0.23 μM and 0.07 μM, respectively). HDACs/EZH2-IN-1 exerts a antiproliferative effect on diffuse large B-cell lymphoma cells harboring an EZH2 mutation and on various acute myeloid leukemia cells. HDACs/EZH2-IN-1 has the ability to induce cell differentiation and Apoptosis.

mTOR/HDAC-IN-1 (Compound 50) is a selective mTOR and HDAC dual inhibitor with IC₅₀ values of 0.49 and 0.91 nM against mTOR and HDAC1, respectively. mTOR/HDAC-IN-1 can be studied as an anti-cancer agent.

HDAC1-IN-3 is a potent Pf HDAC1 inhibitor. HDAC1-IN-3 shows antimalarial activity in wild-type and multidrug-resistant parasite strains. HDAC1-IN-3 shows a significant in vivo killing effect against all life cycles of parasites.

HDAC6/HSP90-IN-2 (compound 6e) is a dual inhibitor of HDAC6 and Hsp90, with IC₅₀s of 105.7 and 61 nM, respectively. HDAC6/HSP90-IN-2 can be used for the research of cancer.

Wee1/HDAC-IN-1 is a dual Wee1/HDAC inhibitor with an IC₅₀ of 1.2 nM for Wee1 and IC₅₀ values of 196 nM for HDAC1, 156 nM for HDAC3, and 55 nM for HDAC6. Wee1/HDAC-IN-1 exhibits strong antiproliferative activity against MV4-11 cells with an IC₅₀ of 0.076 μM. Wee1/HDAC-IN-1 selectively binds to Wee1 and HDACs. Wee1/HDAC-IN-1 interferes with DNA damage repair pathways and induces apoptosis in MV4-11 cells. Wee1/HDAC-IN-1 Wee1/HDAC-IN-1 can be used for the research of acute myeloid leukemia (AML).

CM-545, the cis-isomer of CM-414 (HY-119316), is a dual inhibitor of PDE5, HDAC1, HDAC2, HDAC3, and HDAC6 with pIC₅₀ values of 7.47, 6.65, 6.14, 6.55, and 6.84, repectively.

ZWZH-21 is a selective and orally active HDAC1/2 dual inhibitor with IC₅₀ values of 34 nM for HDAC1 and 41 nM for HDAC2. ZWZH-21 can inhibit HCT116 and SW480 cells growth with IC₅₀ values of 0.524 μM and 1.063 μM, respectively. ZWZH-21 can inhibit proliferation and migration and induces apoptosis in multiple colorectal cancer cells. ZWZH-21 can be used for the research of cancer, such as colorectal cancer.

PI3K/HDAC-IN-5 is a dual PI3K/HDAC inhibitor. PI3K/HDAC-IN-5 inhibits PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ (IC₅₀ values of 25.41, 134.52, 166.75, and 41.58 nM, respectively) and inhibits downstream PI3K/AKT signaling. PI3K/HDAC-IN-5 inhibits HDAC6, HDAC8, and HDAC11 (IC₅₀ values of 29.35, 157.27, and 382.26 nM, respectively), increases α-tubulin and SMC3 acetylation, while not affecting histone H3/H4 acetylation. PI3K/HDAC-IN-5 induces S phase cell cycle arrest and apoptosis, and inhibits the proliferation of cervical cancer cell lines. PI3K/HDAC-IN-5 can be used for research on cervical cancer.

SM-06-09 is a potent, highly selective, orally active tetrazolone-based HDAC6 inhibitor with an IC₅₀ value of 0.49 nM. SM-06-09 promotes tumor-associated macrophage (TAM) polarization toward an antitumor M1-like phenotype and enhances macrophage phagocytosis, antigen presentation, and T-cell activation. SM-06-09 remodels the tumor immune microenvironment, exhibits antitumor activity in melanoma models, and enhances the efficacy of anti-PD-1 immune checkpoint blockade.

ST13, an ortho-hydroxyanilide, is a selective, slow- and tight-binding HDAC1 and HDAC2 inhibitor with IC₅₀s of 23 nM and 49 nM, respectively. ST13 shows a weak inhibition of HDAC3 (IC₅₀ = 4.30 μM) and HDAC6 (IC₅₀ > 10 μM). The induced fit mechanism of ST13 proceeds through a two-step process: first, the enzyme and inhibitor rapidly form a collision complex (EI), which then slowly transforms into the stable complex E*I. ST13 induces apoptosis in cancer cells. ST13 can be used for the study of melanoma and triple-negative breast.

HDAC-IN-88 (Compound HJ-9) is the inhibitor for HDAC that inhibits HDAC6, HDAC1, HDAC2, HDAC8 and HDAC3 with IC₅₀s of 0.226, 1.103, 2.308, 3.255 and 3.864 μM, respectively. HDAC-IN-88 inhibits the proliferation of cancer cell HepG2, HCT116 and MV4-11 with IC₅₀ of 5.47, 9.78 and 0.38 μM, inhibits the migration of HCT116, arrests the cell cycle at G0/G1 phase, and induces apoptosis and autophagy in MV4-11. HDAC-IN-88 reduces ROS level and mitochondrial membrane potential. HDAC-IN-88 exhibits antimalarial activity that inhibits P. falciparum 3D7 with EC₅₀ of 165 nM. HDAC-IN-88 also exhibits anti-angiogenic activity.