2. Cell Cycle/DNA Damage PI3K/Akt/mTOR Epigenetics Apoptosis Metabolic Enzyme/Protease
  3. DNA-PK HDAC Apoptosis Mitochondrial Metabolism DNA/RNA Synthesis
  4. DNA-PK/HDAC6-IN-1

DNA-PK/HDAC6-IN-1 is a selcetive and orally active dual DNA-PK and HDAC6 inhibitor with IC50 values of 84.2 and 64.8 nM. DNA-PK/HDAC6-IN-1 suppresses cancer cells proliferation, induces cancer cell cycle G2/M arrest, apoptosis, and decreases the mitochondrial membrane potential. DNA-PK/HDAC6-IN-1 induces DNA damage and elevates γ-H2AX levels. DNA-PK/HDAC6-IN-1 exhibits antitumor efficacy in AML animal mouse model. DNA-PK/HDAC6-IN-1 can be used for the research of acute myeloid leukemia.

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DNA-PK/HDAC6-IN-1

DNA-PK/HDAC6-IN-1 Chemical Structure

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DNA-PK/HDAC6-IN-1 Related Antibodies

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Description

DNA-PK/HDAC6-IN-1 is a selcetive and orally active dual DNA-PK and HDAC6 inhibitor with IC50 values of 84.2 and 64.8 nM. DNA-PK/HDAC6-IN-1 suppresses cancer cells proliferation, induces cancer cell cycle G2/M arrest, apoptosis, and decreases the mitochondrial membrane potential. DNA-PK/HDAC6-IN-1 induces DNA damage and elevates γ-H2AX levels. DNA-PK/HDAC6-IN-1 exhibits antitumor efficacy in AML animal mouse model. DNA-PK/HDAC6-IN-1 can be used for the research of acute myeloid leukemia[1].

IC50 & Target[1]

HDAC6

64.8 nM (IC50)

In Vitro

DNA-PK/HDAC6-IN-1 (Compound DH-1) potently and balancedly inhibits recombinant DNA-PK (IC50 = 84.2 nM) and HDAC6 (IC50 = 64.8 nM) enzymes in biochemical assays[1].
DNA-PK/HDAC6-IN-1 forms a stable, high-affinity complex with DNA-PK, as confirmed by molecular docking (binding energy = -10.5 kcal/mol) and 100 ns molecular dynamics simulations, with a calculated binding free energy of -10.605 kcal/mol[1].
DNA-PK/HDAC6-IN-1 forms a stable, high-affinity complex with HDAC6, as confirmed by molecular docking (binding energy = -9.6 kcal/mol) and 100 ns molecular dynamics simulations, with a calculated binding free energy of -9.635 kcal/mol[1].
DNA-PK/HDAC6-IN-1 (compound DH-1) (0.1-1 μM) selectively inhibits HDAC6 in HL-60 cells, as shown by concentration-dependent upregulation of acetylated-α-tubulin without affecting acetylated-H3 or acetylated-SMC3 levels[1].
DNA-PK/HDAC6-IN-1 (48 h) potently inhibits the proliferation of Jurkat (IC50 = 0.72 μM) and HL-60 (IC50 = 0.41 μM) cancer cells, while exhibiting minimal toxicity against normal HEK-293 cells (IC50 >20 μM)[1].
DNA-PK/HDAC6-IN-1 (10 μM; 24 h) impairs DNA damage repair in LoVo cells, resulting in elevated γ-H2AX levels[1].
DNA-PK/HDAC6-IN-1 (compound DH-1) (1 μM; 24 h) arrests HL-60 cells in the G2/M phase of the cell cycle[1].
DNA-PK/HDAC6-IN-1 (1 μM; 24 h) induces significant early and late apoptosis in HL-60 cells[1].
DNA-PK/HDAC6-IN-1 (1 μM; 24 h) decreases the mitochondrial membrane potential in HL-60 cells[1].

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

DNA-PK/HDAC6-IN-1 Related Antibodies

Western Blot Analysis[1]

Cell Line: LoVo colorectal cancer cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Significantly elevated γ-H2AX levels (a biomarker of DNA double-strand breaks) compared to repair-only controls.

Immunofluorescence[1]

Cell Line: LoVo colorectal cancer cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Significantly elevated γ-H2AX levels.

Cell Cycle Analysis[1]

Cell Line: HL-60 acute myeloid leukemia cells
Concentration: 1 μM
Incubation Time: 24 h
Result: Increased the proportion of cells in the G2/M phase.
REduced the proportion of cells in the G1 phase.

Apoptosis Analysis[1]

Cell Line: HL-60 acute myeloid leukemia cells
Concentration: 1 μM
Incubation Time: 24 h
Result: Induced significant levels of both early and late apoptosis, with early apoptosis (>20%) and late apoptosis (>10%).
Parmacokinetics
Species Dose Route AUC0-t AUC0-∞ T1/2 CL C0 Cmax F
Rat[1] 2 mg/kg i.v. 970.5 μg/L·h 1291.5 μg/L·h 14.1 h 1.5 L/h/kg 1813.8 μg/L / /
Rat[1] 20 mg/kg p.o. 1932.9 μg/L·h 2073.7 μg/L·h 7.9 h 13.9 L/h/kg / 2633.6 μg/L 14.4 %
In Vivo

DNA-PK/HDAC6-IN-1 (Compound DH-1) (20 mg/kg; i.g.; once daily; 24 consecutive days) exhibits potent antileukemic efficacy in a systemic AML mouse model, achieving a 67.9% tumor growth inhibition rate, reducing leukemic cell burden in bone marrow and spleen, and mitigating organ infiltration with favorable tolerability[1].

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

Animal Model: NOD.Cg-Prkdcscid Il2rgtm1Vst/Vst (NPG) (male, 5-6 weeks old, intravenously inoculated with 5×106 HL-60-Luc-GFP cells)[1]
Dosage: 20 mg/kg
Administration: I.g.; once daily; 24 consecutive days
Result: Achieved a tumor growth inhibition (TGI) rate of 67.9%.
Significantly reduced spleen weight compared to vehicle controls.
Showed a significant reduction in GFP-positive HL-60-luc AML cells in both bone marrow and spleen.
Mitigated leukocyte infiltration in the liver, and normalized splenic morphology relative to vehicle controls.
Molecular Weight

512.60

Formula

C26H36N6O5
SMILES

CC(C=CC(OCCCCCCC(NO)=O)=C1)=C1NC2=NC(N(C3)C4CCOCC4)=C(C=N2)N(C)C3=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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DNA-PK/HDAC6-IN-1 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

DNA-PK/HDAC6-IN-1DNA-PKHDACApoptosisMitochondrial MetabolismDNA/RNA SynthesisDNA-dependent protein kinaseHistone deacetylasesLoVo cellsAML cellsHEK-293 cellsHL-60 cellsacute myeloid leukemiaSprague-Dawley ratsHDAC6Jurkat cellsγ-H2AXInhibitorinhibitorinhibit

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