hdac-8-in-1

HDAC8-IN-1 是一种 HDAC8 抑制剂，在癌细胞系中的 IC50 为 27.2 nM，有抗增殖作用。

HDAC8-IN-11 作为一种PROTAC靶蛋白配体,展示了其在生物医学领域的重要用途.

HDAC8-IN-10 (compound 15),作为一种高效的HDAC8抑制剂,具备7.6 nM的IC50值.它可作为HDAC8靶向蛋白的配体,用于PROTAC YX862的合成.

ROCK HDAC-IN-1（Compound 10h）作为一种抑制剂，通过口服展现出对ROCK HDAC的有效抑制。该化合物针对ROCK1 2和HDAC1 2 3 6 8表现出卓越的抑制效率，其IC50值分别为254.9 nM、58.18 nM和9.09、8.03、6.26、0.41、7.69 nM。此外，ROCK HDAC-IN-1能激活DAMP，尤其增强了钙网蛋白（CRT）的外露和HMGB1的释放，显示其作为免疫性细胞死亡（ICD）诱导剂的潜力。对于乳腺癌细胞，特别是MDA-MB-231细胞，此抑制剂具有抗增殖活性，IC50值为0.37 μM，且能在不产生明显毒性的情况下，抑制肿瘤生长并激活T细胞。

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

Tubulin HDAC-IN-3（compound 12a）为一种高效的tubulin HDAC汇合型抑制剂，能显著破坏微管蛋白聚合（IC50: 5.4 μM），并对HDAC1 8展现强效抑制作用，IC50值分别为0.155 μM和0.177 μM。该化合物通过阻断细胞周期、诱导细胞凋亡（apoptosis）及抑制集落形成以施展其生物学效用。

HDAC-IN-62（Compound 5），是一款针对HDAC6 8 11的HDAC抑制剂，IC50分别为0.78、1.0、1.2μM。该化合物通过诱导自噬（Autophagy）来抑制微胶质细胞的激活，进而抑制一氧化氮产生，显示出抗炎和抗抑郁的效果。此外，HDAC-IN-62还能抑制实验小鼠大脑中的微胶质细胞活化。

HDAC-IN-67 (compound 27f)，作为一种HDAC抑制剂，对HDAC1和HDAC6展现出强效的抑制作用，其IC50值仅为22 nM和8 nM。该化合物能够有效抑制细胞增殖并且诱导细胞凋亡（apoptosis），显示出潜在的抗肿瘤活性。

AES-350 是一种具有口服活性HDAC6抑制剂，IC50和Ki 分别为 0.0244 μM 和 0.035 μM。它对 HDAC3、8 和 11 的 IC50值分别为 0.187、0.245和大于1μM。它通过抑制 HDAC 诱导 AML 细胞凋亡，可研究急性髓系白血病。