DNA-PK/HDAC6-IN-2
DNA-PK/HDAC6-IN-2 is an orally active and selective dual-target inhibitor of DNA-PK and HDAC6, with an IC50 of 34.22 nM for DNA-PK and an IC50 of 241.2 nM for HDAC6. DNA-PK/HDAC6-IN-2 upregulates Ac‑α‑tubulin, inhibits p‑DNA‑PK, and increases γ‑H2AX. DNA-PK/HDAC6-IN-2 exhibits antiproliferative activity against multiple solid tumor cell lines, induces apoptosis and cell cycle arrest, and inhibits migration and invasion. DNA-PK/HDAC6-IN-2 has in vivo antitumor efficacy in melanoma and breast cancer models and enhances the efficacy of Doxorubicin (HY-15142A). DNA-PK/HDAC6-IN-2 can be used for research on various cancers such as melanoma, breast cancer, and colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 3107156-58-8
- Formula: C23H30N6O5
- Molecular Weight:470.52
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
HDAC6 241.2 nM (IC50) |
α-Tubulin |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| 4T1 | IC50 |
24.96 μM
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Antiproliferative activity against mouse 4T1 cells assessed as IC50.
Antiproliferative activity against mouse 4T1 cells assessed as IC50.
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42743643 |
| SK-OV-3 | IC50 |
18.42 μM
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Antiproliferative activity against human SK-OV-3 cells assessed as IC50.
Antiproliferative activity against human SK-OV-3 cells assessed as IC50.
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42743643 |
| HCT-116 | IC50 |
22.29 μM
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Antiproliferative activity against human HCT-116 cells assessed as IC50.
Antiproliferative activity against human HCT-116 cells assessed as IC50.
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42743643 |
| B16-F10 | IC50 |
19.18 μM
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Antiproliferative activity against mouse B16-F10 cells assessed as IC50.
Antiproliferative activity against mouse B16-F10 cells assessed as IC50.
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42743643 |
In Vitro
DNA-PK/HDAC6-IN-2 (10-20 μM; 0-24 h) inhibits B16-F10 migration and invasion, and upregulates E-cadherin while downregulating N-cadherin in B16-F10 cells[1].
DNA-PK/HDAC6-IN-2 (1.25-20 μM; 24 h) upregulated Ac-α-tubulin in HCT-116 and B16-F10 cells without affecting Ac-H3, total H3, or total α-tubulin, and reduced PD-L1 in B16-F10 cells[1].
DNA-PK/HDAC6-IN-2 (20 μM; 30 min-16 h) in combination with Doxorubicin (HY-15142A) increases γ-H2AX and decreases p-DNA-PK in B16-F10 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:B16-F10 cells
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Concentration:10, 20 μM
20 μM (wound healing assay) -
Incubation Time:24 h
0, 12, 24 h (wound healing assay) -
Result:Inhibited B16-F10 migration and invasion, and upregulates E-cadherin while downregulating N-cadherin in B16-F10 cells.
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Cell Line:B16-F10 cells
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Concentration:20 μM
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Incubation Time:24 h
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Result:Induced apoptosis in B16-F10 cells in a concentration-dependent manner: 32.0% apoptotic cells at 5 μM and 48.7% at 20 μM.
Induced significant G2/M phase arrest.
Upregulated cleaved caspase-3, cleaved PARP, and P21 in a concentration-dependent manner.
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Cell Line:HCT-116 and B16-F10 cells
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Concentration:1.25, 2.5, 5.0, 10 μM (Western blot for Ac-α-tubulin/Ac-H3/H3/α-tubulin in HCT-116 and B16-F10)
2.5, 5, 10, 20 μM (Western blot for Ac-α-tubulin and PD-L1 in B16-F10) -
Incubation Time:24 h
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Result:Upregulated Ac‑α‑tubulin in HCT‑116 and B16‑F10 cells while exerting no obvious influence on Ac‑H3, total H3, or total α‑tubulin.
Produced concentration‑dependent Ac‑α‑tubulin expression and reduced PD‑L1 expression similarly to ACY‑1215 in B16‑F10 cells.
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Cell Line:B16-F10 cells
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Concentration:20 μM; Doxorubicin (HY-15142A) 100 nM
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Incubation Time:30 min, 2, 4, 8, 16 h
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Result:Combined with Doxorubicin elevates γ-H2AX and reduces p-DNA-PK in B16-F10 cells.
Parmacokinetics
In Vivo
DNA-PK/HDAC6-IN-2 (25 mg/kg; i.p.; QD) enhanced the efficacy of Doxorubicin (HY-15142A) in the 4T1-Luc breast cancer model, achieving a TGI of 73.6% in combination therapy[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 4 weeks old, 3 × 105 B16-F10 cells)[1]
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Dosage:50 mg/kg
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Administration:i.p.; daily; for two weeks
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Result:Suppressed tumor volume with a tumor growth inhibition rate (TGI) of 78.2%.
In melanoma tumor tissues, DH-6 increased intratumoral Ac-α-tubulin and γ-H2AX levels and reduced p-DNA-PK levels, with no obvious influence on total DNA-PK or Ac-H3 expression.
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Animal Model:Balb/c (female, 6 weeks old, 100 μL of
4T1-Luc cells into the armpit)[1] -
Dosage:25 mg/kg (DH-6); 2.5 mg/kg (Doxorubicin)
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Administration:DH-6: i.p.; QD; 14 days; Doxorubicin: i.v.; days 1 and 8
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Result:Reduced tumor volume relative to doxorubicin monotherapy upon combination of DH‑6 plus doxorubicin, achieving a TGI of 73.6%.
Observed a marked decrease in tumor weight.
Confirmed enhanced doxorubicin therapeutic efficacy by fluorescence imaging of mouse tumors.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Cell migration
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Protocol for Cell Cycle
- Cell invasion
- Breast Cancer Modeling
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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CAS No. 3107156-58-8
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Molecular Weight 470.52
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Formula C23H30N6O5
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SMILES
CC1=C(C=C(C=C1)OCCCCC(NO)=O)NC2=NC=C3C(N(C(N3C)=O)C4CCOCC4)=N2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DNA-PK/HDAC6-IN-2 Related Classifications
HY-189675 Related Classifications
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