PROTAC Aurora A Degrader-1
PROTAC Aurora A Degrader-1 is an orally active and blood-brain barrier-permeable selective Aurora A PROTAC degrader. PROTAC Aurora A Degrader-1 induces AURKA degradation with a DC50 of 6 nM in IMR32 cells (Dmax = 95%), eliminates both the kinase catalytic activity and N-Myc stabilizing scaffolding function of Aurora A, induces DNA damage, G2/M arrest and apoptosis, and shows antiproliferative activity. PROTAC Aurora A Degrader-1 is applicable to the research of neuroblastoma and small cell lung cancer.
(Pink: Aurora A ligand (HY-10971); Blue: Cereblon ligand (HY-103597); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3115344-59-4
- Formula: C38H43ClN10O3
- Molecular Weight:723.27
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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]|
Aurora A |
Cereblon |
In Vitro
PROTAC Aurora A Degrader-1 (serial concentration gradient; 7 days) dose-dependently suppresses proliferation of MV4-11, IMR32, SK-N-BE(2) neuroblastoma and SCLC cells, with GI50 values as low as 5.6 nM (H82 SCLC cell line)[1].
PROTAC Aurora A Degrader-1 (3 μM; 24 h) reduces intracellular N-Myc protein level by eliminating Aurora A scaffolding function for N-Myc stabilization, without changing MYCN mRNA transcription[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SK-N-BE(2), IMR32, SCLC
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of endogenous Aurora A in MYCN-amplified neuroblastoma with DC50 = 6 nM and Dmax = 95%.
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Cell Line:SK-N-BE(2), SCLC
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Concentration:0.5, 1, 3 μM
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Incubation Time:24-48 h
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Result:Triggered G2/M cell cycle arrest and tumor cell apoptosis, upregulates cleaved Caspase-3 and cleaved PARP protein expression, and elevates intracellular DNA damage response level.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 | C0 | AUClast | Cmin | Tmax | Cmax | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 17.5 mL/min/kg | 4.78 L/kg | 5.51 h | 498 ng/mL | 928 ng·h/mL | 3.52 ng/mL | / | / | / |
| Rat[1] | 1 mg/kg | i.v. | 27 mL/min/kg | 3.12 L/kg | 3.20 h | 596 ng/mL | 620 ng·h/mL | 0.26 ng/mL | / | / | / |
| Dog[1] | 1 mg/kg | i.v. | 14 mL/min/kg | 12 L/kg | 13 h | 382 ng/mL | 917 ng·h/mL | 11.4 ng/mL | / | / | / |
| Mice[1] | 10 mg/kg | p.o. | / | / | / | / | 5410 ng·h/mL | 6.54 ng/mL | 1 h | 796 ng/mL | 58 % |
| Rat[1] | 10 mg/kg | p.o. | / | / | / | / | 4514 ng·h/mL | 4.70 ng/mL | 8 h | 365 ng/mL | 73 % |
| Dog[1] | 10 mg/kg | p.o. | / | / | / | / | 10091 ng·h/mL | 197 ng/mL | 4.67 h | 916 ng/mL | 71 % |
In Vivo
PROTAC Aurora A Degrader-1 significantly inhibits tumor volume growth and prolongs overall survival of neuroblastoma and SCLC xenograft mice, achieves durable tumor regression and extends survival in IMR-32 models, extends median survival to 34 days compared to 17 days for the AURKA inhibitor LY3295668 (HY-114258) and vehicle control in H82 SCLC models, and shows no significant body weight loss or severe myelosuppression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:IMR32 Neuroblastoma Xenograft[1]
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Dosage:60 mg/kg
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Administration:p.o.; once daily
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Result:Induced rapid and sustained AURKA degradation.
Reduced phosphorylated Aurora A and N-Myc protein in tumor tissue.
Induced sustained DNA damage and G2/M arrest.
Triggered massive tumor cell apoptosis.
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Animal Model:H82 SCLC Xenograft[1]
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Dosage:60 mg/kg
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Administration:p.o.; once daily
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Result:Inhibited tumor volume growth and prolongs overall survival.
Achieved durable tumor regression.
Extended median survival to 34 days compared to 17 days for the AURKA inhibitor LY3295668 and vehicle control.
Showsed no significant body weight loss or severe myelosuppression.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Apoptosis Solutions
- Protocol for Cell Cycle
- Genotoxicity/Mutagenicity Study
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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CAS No. 3115344-59-4
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Molecular Weight 723.27
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Formula C38H43ClN10O3
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SMILES
CC1=NN(C=C1C2=NC3=C(N2)N=CC(Cl)=C3OC4=CC=C(C=C4)N5CCN(C[C@@H]5C)CC6CCN(CC6)C7=CC=C(C=C7)N8CCC(NC8=O)=O)C
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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)
PROTAC Aurora A Degrader-1 Related Classifications
HY-181568 Related Classifications
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