HDAC-IN-104

HDAC-IN-104 (compound 6k) (50-200 nM) exhibits superior HDAC inhibitory activity to the pan-HDAC inhibitor Vorinostat (SAHA) (HY-10221), with an IC₅₀ value of 25 nM in the HeLa nuclear extract-based assay^[1].
HDAC-IN-104 (30 min) demonstrates potent and selective HDAC1 inhibitory activity with an IC₅₀ of 32 nM; it exhibits 3-fold (IC₅₀= 110 nM), 9-fold (IC₅₀ = 290 nM), and 17-fold (IC₅₀ = 570 nM) selectivity over HDAC2, HDAC3, and HDAC8, respectively, 4-fold selectivity over HDAC6 (IC₅₀ = 140 nM), and 60-fold selectivity over HDAC10 (IC₅₀ = 2 μM), while displaying minimal inhibitory activity against class IIa HDACs (HDAC5: IC₅₀ = 6.4 μM; HDAC7: IC₅₀ = 11 μM) and class IV HDAC (HDAC11: IC₅₀ = 9.3 μM)^[1].
HDAC-IN-104 (48 h) exhibits superior antiproliferative activity to SAHA across all tested cancer cell lines, with IC₅₀s of 0.34 μM (KG-1), 0.20 μM (Molm-13), 0.16 μM (MV4-11), 0.42 μM (OCL-AML), 0.89 μM (THP-1), and 0.76 μM (PC-9), showing the most potent inhibitory activity against FLT3-ITD-mutated MV4-11 cells^[1].
HDAC-IN-104 (0.25-0.5 μM; 24 h) increases the levels of acetylated histone H3 (a substrate of class I HDACs) and acetylated α-tubulin (a substrate of HDAC6) in a dose-dependent manner in MV4-11 cells, suggesting superior intracellular exposure or cell membrane permeability that compensates for its slightly weaker enzymatic activity against HDAC6 in MV4-11 cells ^[1].
HDAC-IN-104 (0.25-0.5 μM; 12-24 h) induces significant early apoptosis in MV4-11 cells after 12 h of treatment and drives the majority of cells into late apoptosis by 24 h, with superior efficacy to SAHA across various concentrations, achieving approximately 50% late apoptosis at 0.5 μM in MV4-11 cells^[1].
HDAC-IN-104 (0.5 μM; 24 h) up-regulates 6,804 genes and down-regulates 4,361 genes in MV4-11 cells, including key metabolic genes involved in glycolysis (HK2, GPI, PFKL, LDHA) and OXPHOS (NDUF, SDHA, COX, ATP), and negatively enriches the AML and OXPHOS gene sets, indicating suppression of tumor proliferation-related genes and disruption of energy metabolism^[1].
HDAC-IN-104 (0.5 μM; 24 h) modulates multiple oncogenic signaling pathways, including PI3K‑AKT, MAPK, and Ras pathways, as well as metabolic pathways such as OXPHOS, fatty acid metabolism, and glycolysis^[1].
HDAC-IN-104 (0.1-1 μM; 48 h) shows strong synergistic antitumor activity when combined with Quizartinib (AC220) (HY-13001) in MV4‑11 cells, with the combination inducing significantly more cell death than either monotherapy^[1].
HDAC-IN-104 (0.5 μM; 24 h) exerts synergistic antitumor activity by suppressing PI3K‑AKT signaling, which in turn inhibits glycolysis and OXPHOS and disrupts the metabolic plasticity of MV4‑11 cells and these effects are potentiated when combined with Quizartinib^[1].
HDAC-IN-104 (0.5 μM; 24 h) inhibits glycolysis in MV4‑11 cells, as evidenced by reduced ECAR, glucose uptake, lactate production, and ATP levels and these effects are potentiated when combined with Quizartinib^[1].
HDAC-IN-104 (0.5 μM; 24 h) suppresses OXPHOS in MV4‑11 cells, as evidenced by reduced oxygen consumption rate (OCR), increased mitochondrial ROS accumulation, and decreased NAD⁺/NADH ratio and these effects are potentiated when combined with Quizartinib^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.