HDAC-IN-104
HDAC-IN-104 is a potent and selective class I Histone deacetylases (HDAC) inhibitor with an IC50 of 25 nM. HDAC-IN-104 exerts potent antiproliferative and antitumor effects by inhibiting glycolysis and OXPHOS via blockade of the PI3K/AKT signaling pathway, and these effects are synergistically enhanced when combined with the FMS-like tyrosine kinase 3 (FLT3) inhibitor Quizartinib (AC220) (HY-13001). HDAC-IN-104 induces significant early and late apoptosis. HDAC-IN-104 can be used for acute myeloid leukemia (AML) research.
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- Formule: C21H24N4O2S
- Masse moléculaire:396.51
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Activité biologique
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HDAC 25 nM (IC50) |
HDAC1 32 nM (IC50) |
HDAC2 110 nM (IC50) |
HDAC3 290 nM (IC50) |
HDAC5 6.4 μM (IC50) |
HDAC6 140 nM (IC50) |
HDAC7 11 μM (IC50) |
HDAC8 570 nM (IC50) |
HDAC10 2.0 μM (IC50) |
HDAC11 9.3 μM (IC50) |
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.
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Cell Line:MV4-11 cells
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Concentration:0.5 μM
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Incubation Time:24 h
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Result:Downregulated the level of HK2.
Significantly inhibited LDHA expression, and this effect was markedly intensified in the combination group with Quizartinib.
Effectively reduced the phosphorylation of PI3K and AKT, and this blockade was exacerbated by the combination with Quizartinib.
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Cell Line:MV4-11 cells
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Concentration:0.25 μM, 0.5 μM
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Incubation Time:12-24 h
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Result:Induced significant early apoptosis in MV4-11 cells after 12 h of treatment, as measured by JC-1 staining.
Exhibited superior pro-apoptotic efficacy to SAHA across various concentrations. Drove the majority of cells into late apoptosis by 24 h, as measured by Annexin V-FITC/PI dual staining.
Induced late apoptosis in approximately 50% of MV4-11 cells at a concentration of 0.5 μM.
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Cell Line:MV4-11 cells
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Concentration:0.25 μM, 0.5 μM
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Incubation Time:24 h
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Result:Increased 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.
Exhibited a stronger ability to increase histone H3 acetylation than SAHA, while its effect on α-tubulin acetylation was comparable to that of SAHA.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (6 weeks old) were subcutaneously injected with MV4 11 cells (1 × 107) suspended in a 1:1 mixture of serum free RPMI 1640 and matrigel into the flank to establish the xenograft model[1].
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Dosage:30 mg/kg
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Administration:once a day; i.p.; 21 days
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Result:Exhibited significant antitumor activity in the MV4‑11 xenograft model in monotherapy compared with the vehicle control group.
Elicited a much more potent response, resulting in marked tumor volume regression when combined with Quizartinib.
Achieved a tumor growth inhibition (TGI) rate of 70.8%, significantly surpassing 6k monotherapy (44.3%) and Quizartinib monotherapy (51.3%) when combined with quizartinib.
Demonstrated a good safety profile, as no significant body weight loss or organ toxicity was observed during the treatment period when combined with Quizartinib.
Verified the robust inhibitory activity and selectivity of 6k against class I HDACs.
Down‑regulated LDHA and p‑AKT levels in excised tumor tissues, and this effect was most significant in the combination group, confirming its on‑target mechanism in vivo.
Chemical Information
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Masse moléculaire 396.51
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Formule C21H24N4O2S
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SMILES
O=C(/C=C/C1=CC=C(CN2C3=CC=CC=C3N=C2SCCN(C)C)C=C1)NO
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HDAC-IN-104 Related Classifications
HY-184574 Related Classifications
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