hdac8-in-3

HDAC8-IN-3 (compound P19) is a highly potent HDAC8 inhibitor with an IC50 value of 9.3 μM, inducing thermal stabilization, cytotoxicity, and apoptosis specifically in leukemic cell lines [1].

HDAC11-IN-2 (compound B6) is a highly selective inhibitor of Histone Deacetylase 11 (HDAC11). It demonstrates IC50 values of 51.1 ×10^-3 μM for HDAC11 and 5 μM for HDAC8. HDAC11-IN-2 reduces de novo lipogenesis (DNL) and enhances fatty acid oxidation, which alleviates hepatic lipid accumulation and pathological symptoms in MASLD mice. By inhibiting HDAC11, HDAC11-IN-2 enhances the phosphorylation of AMPKα1 at the Thr172 site, thereby modulating de novo lipogenesis and fatty acid oxidation in the liver.

CS4 is a selective HDAC inhibitor, with IC50 values for HDAC1, HDAC6, HDAC8, HDAC4, and HDAC11 reported as 38 nM, 12 nM, 5.8 μM, 19 μM, and 61 μM, respectively. It enhances the acetylation of α-tubulin and histone 3 (histone 3). Additionally, CS4 activates PPARγ and blocks glycolysis (glycolysis). It induces cell cycle arrest at the G2 phase and triggers apoptosis (apoptosis), exhibiting anticancer effects both in vitro and in vivo.

HDAC8-IN-6 (compound 3) is a potent inhibitor of HDAC8 with an IC50 of 5.1 μM and exhibits cytotoxicity.

HDAC8-IN-14 is a curcumin derivative serving as a selective HDAC8 inhibitor with a Ki of 9 nM. It induces reactive oxygen species (ROS) production, disrupts mitochondrial membrane potential, and promotes apoptosis. Furthermore, HDAC8-IN-14 significantly triggers cell accumulation in the sub-G0/G1 phase, indicative of apoptosis or necroptosis. It upregulates cytochrome c, cleaved caspase-3, and pro-apoptotic protein Bak expression, while maintaining anti-apoptotic protein Bcl-2 levels unchanged, making it a valuable compound for leukemia research.

HDAC10-IN-3 (Compound 2a) is a potent inhibitor of HDAC10, with IC50 values of 0.41, 37, 350, and 4500 nM for HDAC10, HDAC6, HDAC8, and HDAC1, respectively. It exhibits moderate cytotoxicity against KB and SK-OV-3 cells but shows no significant cytotoxicity against most cancer cell lines. HDAC10-IN-3 can be utilized in cancer research.

PROTACHDAC8 Degrader-3 (Compound BP1) is a potent and selective HDAC8 PROTAC degrader with a DC50 of 20 nM. It exhibits IC50 values of 0.46 μM for HDAC8 and 7.5 μM for CRBN. PROTACHDAC8 Degrader-3 shows strong antiproliferative activity against MM.1S and HL-60 cells, and it is applicable in the study of multiple myeloma and acute myeloid leukemia.

HDAC6-IN-3 (Compound 14) is a potent anti-prostate cancer agent that acts as an orally active inhibitor of HDAC6. It has IC50 values ranging from 0.02-1.54 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10. Additionally, HDAC6-IN-3 also demonstrates effective inhibition of MAO-A (IC50 = 0.79 μM) and LSD1 [1].

HDAC-IN-47 is an orally active histone deacetylase (HDAC) inhibitor, with IC50 values of 19.75 nM, 57.8 nM, 40.27 nM, 5.63 nM, and 302.73 nM for HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, respectively. HDAC-IN-47 can block the cell cycle in the G2/M phase, inhibit autophagy, induce apoptosis via the Bax/Bcl-2 and caspase-3 pathways, and exhibits anti-cancer activity in vivo.

Tubulin/HDAC-IN-3 (compound 12a) is a potent dual inhibitor of tubulin polymerization and HDAC1/8, with IC50 values of 5.4 μM for tubulin polymerization, and 0.155 and 0.177 μM for HDAC1 and HDAC8, respectively. It obstructs the cell cycle, triggers apoptosis, and suppresses colony formation [1].