hdac-in-20

HDAC-IN-20 is used as an HDAC inhibitor that acts by preventing HDAC-mediated diseases.

BG45 is an HDAC I type inhibitor with IC50 of 289 nM, 2.0 μM, 2.2 μM and >20 μM for HDAC3/1/2/6 in cell-free assays, respectively.

LSD1/HDAC-IN-2 (Compound 20c) acts as an inhibitor targeting both LSD1 and several HDACs, specifically HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with IC50 values of 39.0, 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively. This compound effectively inhibits the proliferation of cancer cells, notably colorectal cancer cells. LSD1/HDAC-IN-2 induces cell cycle arrest at the G2/M phase, inhibits cell migration, and triggers apoptosis in HCT-116 and HT-29 cells. Additionally, it demonstrates antitumor activity in mouse models without causing significant toxicity at a dose of 20 mg/kg.

HDAC/HSP90-IN-1 (compound 20) is a potent dual inhibitor targeting HDAC (IC50 = 194 nM) and HSP90 (HSP90α IC50 = 153 nM). It induces the expression of HSP70, downregulates HSP90 substrate proteins, and enhances the acetylation of α-tubulin and histone H3 in cancer cells. Additionally, HDAC/HSP90-IN-1 reduces PD-L1 expression in IFN-γ-treated H1975 cells. This compound is applicable in research on cancers such as lung and colon cancer.

FLT3/HDAC-IN-3 is a dual inhibitor targeting both FLT3 and HDAC. It shows potent inhibition of FLT3 (IC50 = 14 nM), HDAC1 (IC50 = 27 nM), HDAC6 (IC50 = 20 nM), and FLT3D853Y (IC50 = 55 nM), while exhibiting weak activity against HDAC8 and no activity against HDAC4. The compound is characterized by kinase selectivity, plasma stability, and stability in human liver microsomes. It demonstrates antiproliferative effects in various hematologic malignancy cell lines. In the Jeko-1 xenograft model, FLT3/HDAC-IN-3 exhibits inhibitory effects with no significant toxicity observed, making it useful for research in hematologic malignancies.

HDAC/HSP90-IN-4 significantly inhibited HDAC and HSP90 activity, with compound 20 (HDACIC50= 194 nM; HSP90αIC50= 153 nM) and compound 26 ((HDACIC50= 360 nM; HSP90αIC50= 77 nM) having the strongest HDAC and HSP90α inhibition. effect. Both compounds induced HSP90 expression and down-regulated HSP90 client proteins, which play an important role in the regulation of cancer cell survival and invasion.

S-(N-Methylsulfinylbutylthiocarbamoyl)-L-cysteine (SFN-Cys) is an isothiocyanate derivative, functioning as an active metabolite of sulforaphane, a class I and II histone deacetylase (HDAC) inhibitor, and anticancer agent. This compound is generated from sulforaphane through intermediates - DL-sulforaphane glutathione and sulforaphane cysteinylglycine - via the mercapturic acid pathway enzymes. At a concentration of 20 µM, SFN-Cys diminishes invasion and migration of U87MG and U373 MG glioblastoma cells as observed in wound healing and chamber assays. Furthermore, at 45 µM, it significantly lowers the expression of α-tubulin, βIII-tubulin, stathmin 1, and X-linked inhibitor of apoptosis (XIAP), and also reduces cell density in paclitaxel-resistant A549 lung cancer cells (A549/T). Additionally, when used at 30 µM, SFN-Cys prompts apoptosis and cell cycle arrest at the G2/M phase in U87MG and U373 MG cells.

HDAC-IN-71 (Compound 17q), a potent HDAC inhibitor, exhibits IC 50 values of 12.6 nM for HDAC1, 14.1 nM for HDAC2, 20 nM for HDAC3, 3 nM for HDAC6, and 72 nM for HDAC10. This compound induces apoptosis and is utilized in cancer research [1].