Aurora A/HDAC-IN-1
Aurora A/HDAC-IN-1 is an orally active dual inhibitor of Aurora A and pan-HDAC (IC50 = 5.61 μM and 0.31 μM). Aurora A/HDAC-IN-1 induces apoptosis and G2/M cell cycle arrest through downregulating p-Aurora A and increasing Ac-H3 and Ac-α-tubulin acetylation, and exhibits broad-spectrum antiproliferative activity. Aurora A/HDAC-IN-1 can be used for research on leukemia and colorectal cancer.
For research use only. We do not sell to patients.
- Formula: C26H25ClN4O4
- Molecular Weight:492.95
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Biological Activity
Description
Aurora A/HDAC-IN-1 is an orally active dual inhibitor of Aurora A and pan-HDAC (IC50 = 5.61 μM and 0.31 μM). Aurora A/HDAC-IN-1 induces apoptosis and G2/M cell cycle arrest through downregulating p-Aurora A and increasing Ac-H3 and Ac-α-tubulin acetylation, and exhibits broad-spectrum antiproliferative activity. Aurora A/HDAC-IN-1 can be used for research on leukemia and colorectal cancer[1].
IC50 & Target
[1]|
Aurora A 5.61 μM (IC50) |
HDAC 0.31 μM (IC50) |
α-Tubulin |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| Jurkat | IC50 |
0.69 μM
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Antiproliferative activity against human Jurkat cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against human Jurkat cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
| HCT-116 | IC50 |
1.84 μM
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Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
| HeLa | IC50 |
7.09 μM
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Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
| HepG2 | IC50 |
7.27 μM
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Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
| MCF7 | IC50 |
4.17 μM
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Antiproliferative activity against human MCF-7 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against human MCF-7 cells assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
| HUVEC | IC50 |
8.78 μM
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Antiproliferative activity against normal human HUVECs assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
Antiproliferative activity against normal human HUVECs assessed as reduction in cell viability incubated for 48 hrs by CCK-8 assay.
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42614924 |
In Vitro
Anti-cancerApoptosisCell Cycle RegulationOthers
Anti-cancer
Aurora A/HDAC-IN-1 (compound Z20) (various concentrations; 48 h) exhibits potent broad-spectrum antiproliferative activity against Jurkat, HCT-116, HeLa, HepG2, and MCF-7 cell lines, with the highest activity against Jurkat cells (IC50 = 0.69 μM) and a wider therapeutic window than SAHA[1].
Aurora A/HDAC-IN-1 (0.03125-2 μM; 24 h) specifically downregulates p-Aurora A and increases Ac-H3 and Ac-α-tubulin levels in a concentration-dependent manner in both Jurkat and HCT116 cells, without affecting other Aurora family members or total Aurora protein levels[1].
Aurora A/HDAC-IN-1 (0.03125-2 μM; 24 h) specifically downregulates p-Aurora A and increases Ac-H3 and Ac-α-tubulin levels in a concentration-dependent manner in both Jurkat and HCT116 cells, without affecting other Aurora family members or total Aurora protein levels[1].
Apoptosis
Anti-cancer
Cell Cycle Regulation
Anti-cancer
Aurora A/HDAC-IN-1 (0.0625-1 μM; 48 h) induces G2/M phase arrest in Jurkat and HCT116 cells in a dose-dependent manner[1].
Others
Aurora A/HDAC-IN-1 (10 μM; 90 min) exhibits low to moderate inhibitory activity against Aurora A kinase with an IC50 of 5.61 μM[1].
Aurora A/HDAC-IN-1 (10 μM; 20 min) potently inhibits total HDAC enzyme activity with an IC50 of 0.31 μM[1].
Aurora A/HDAC-IN-1, as a pan-HDAC inhibitor, exhibits comparable inhibitory activity against class I (HDAC1, 2, 3) and class IIb (HDAC6, 10) subtypes, with IC50 values in the nanomolar range[1].
Aurora A/HDAC-IN-1 binds stably to both Aurora A and HDAC proteins, with binding free energies of −58.31 kcal mol-1 and −35.29 kcal mol-1, respectively[1].
Aurora A/HDAC-IN-1 (100 μM; 0-60 min) exhibits a short half-life (17.6 min) and a high intrinsic clearance (0.08 mL min-1 mg-1) in human liver microsomes, indicating rapid metabolism[1].
Aurora A/HDAC-IN-1 (10 μM; 20 min) potently inhibits total HDAC enzyme activity with an IC50 of 0.31 μM[1].
Aurora A/HDAC-IN-1, as a pan-HDAC inhibitor, exhibits comparable inhibitory activity against class I (HDAC1, 2, 3) and class IIb (HDAC6, 10) subtypes, with IC50 values in the nanomolar range[1].
Aurora A/HDAC-IN-1 binds stably to both Aurora A and HDAC proteins, with binding free energies of −58.31 kcal mol-1 and −35.29 kcal mol-1, respectively[1].
Aurora A/HDAC-IN-1 (100 μM; 0-60 min) exhibits a short half-life (17.6 min) and a high intrinsic clearance (0.08 mL min-1 mg-1) in human liver microsomes, indicating rapid metabolism[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis[1]
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Cell Line:Jurkat and HCT116
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Concentration:0.25, 0.5, 1, 2, and 4 μM (Jurkat); 0.5, 1, 2, 4, and 8 μM (HCT116)
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Incubation Time:48 h
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Result:Induced total apoptotic ratios of 13.39%, 22.2%, 48%, 97.56%, and 98.7% in Jurkat cells at 0.25, 0.5, 1, 2, and 4 μM, respectively.
Induced total apoptotic ratios of 9.68%, 18.46%, 39.6%, 50.6%, and 53.3% in HCT116 cells at 0.5, 1, 2, 4, and 8 μM, respectively.
Cell Cycle Analysis[1]
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Cell Line:Jurkat and HCT116
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Concentration:0.0625, 0.125, 0.25, 0.5, and 1 μM
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Incubation Time:48 h
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Result:Increased the percentage of Jurkat cells arrested at the G2/M phase to 29.8%, 35%, 35.2%, 36%, and 37.1% at 0.0625, 0.125, 0.25, 0.5, and 1 μM, respectively.
Western Blot Analysis[1]
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Cell Line:Jurkat and HCT116
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Concentration:0.03125, 0.0625, 0.125, 0.25, and 0.5 μM (for p-Aurora and total Aurora proteins); 0.125, 0.25, 0.5, 1, and 2 μM (for Ac-H3 and Ac-α-tubulin); gradient concentrations (HCT116)
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Incubation Time:24 h
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Result:Significantly downregulated p-Aurora A at 0.25 μM.
Did not significantly change p-Aurora B, p-Aurora C, total Aurora A, and total Aurora B levels.
Increased Ac-H3 and Ac-α-tubulin levels in a concentration-dependent manner.
Induced identical regulatory trends in HCT116 cells.
Parmacokinetics
In Vivo
Anti-cancerApoptosisCytokines & Chemokines
Anti-cancer
Apoptosis
Cytokines & Chemokines
The in vivo antitumor efficacy of Aurora A/HDAC-IN-1 (compound Z20) (30-60 mg/kg; p.o.; once daily; for 16 consecutive days) is suboptimal, with TGI rates of 43.74% and 47.24% at doses of 30 mg/kg and 60 mg/kg, respectively, despite its ability to induce tumor cell apoptosis and inhibit proliferation without significant organ toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOG mice (six-week-old, female)[1]
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Dosage:30; 60 mg/kg
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Administration:i.g.; once daily; 16 consecutive days
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Result:Inhibited tumor growth with TGI rates of 43.74% and 47.24% at 30 mg/kg and 60 mg/kg, respectively.
Induced tumor cell apoptosis and inhibited proliferation.
Did not cause significant organ toxicity.
Related Protocols :
Chemical Information
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Molecular Weight 492.95
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Formula C26H25ClN4O4
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SMILES
ClC(C(OC1=NC=CC=C1)=C2)=CC=C2C3=CC(C(NCCCCC(NO)=O)=O)=C(C)C4=C3C=CN4
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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
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Aurora A/HDAC-IN-1 Related Classifications
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