HDAC8 Inhibitor

HDAC-IN-36 (compound 23 g) is an orally active and potent HDAC (histone deacetylase) inhibitor, with an IC₅₀ of 11.68 nM (HDAC6). HDAC-IN-36 promotes apoptosis, autophagy and suppresses migration. HDAC-IN-36 shows anti-tumor and anti-metastatic activity, and can be used for breast cancer research.

HDAC8-IN-16 is a selective histone deacetylase 8 (HDAC8) inhibitor with an IC₅₀ of 0.16 μM. HDAC8-IN-16 induces cell apoptosis, triggers G₂/M phase cell cycle arrest, and moderately inhibits cancer cell proliferation. HDAC8-IN-16 is applicable to relevant research on colorectal cancer.

HDAC-IN-39 (compound 16c) is a potent HDAC inhibitor, with IC₅₀ values of 1.07 μM (HDAC1), 1.47 μM (HDAC2), and 2.27 μM (HDAC3), respectively. HDAC-IN-39 also significantly inhibits microtubule polymerization. HDAC-IN-39 induces cell cycle arrest at the G2/M phase. HDAC-IN-39 displays promising anticancer activity against resistant cancer cells.

NMDAR/HDAC-IN-1 (Compound 9d) is a dual NMDAR and HDAC inhibitor with a K_i of 0.59 μM for NMDAR and IC₅₀ values of 2.67, 8.00, 2.21, 0.18 and 0.62 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8, respectively. NMDAR/HDAC-IN-1 efficiently penetrates the blood brain barrier.

DS-103 is an inhibitor for HDAC that inhibits HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8 with IC₅₀s of 0.029, 0.123, 0.022, 0.367 and 9.26 μM, respectively. DS-103 inhibits Plasmodium falciparum 3D7 with IC₅₀ of 5.08 μM. DS-103 exhibits cytotoxicity in cells A2780 and Cal27 with IC₅₀ of 1.48 μM and 1.47 μM, reverses Cisplatin (HY-17394) resistance in A2780 and Cal27 with IC₅₀ of 4.62 μM and 2.23 μM. DS-103 exhibits synergistic effect with Cisplatin (HY-17394), enhances Cisplatin-induced apoptosis.

TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC₅₀ of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.

HDAC10-IN-2 (compound 10c) is a potent and highly selective HDAC10 inhibitor, with an IC₅₀ of 20 nM. HDAC10-IN-2 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.

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.

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.

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.

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).

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.

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.

HDAC6-IN-85 is a selective HDAC6 inhibitor, with pIC₅₀ values of 5.4, 5.5, 5.9, and 4.8 against rHDAC1, rHDAC3, rHDAC6, and rHDAC8, respectively. HDAC6-IN-85 can be used in the research of cervical cancer, lung cancer, and colon cancer.