HLB-0532259
Based on 1 Customer Validation
HLB-0532259 is a Aurora-A/N-Myc PROTAC degrader, with a DC50 of 20.2 nM against Aurora-A in MCF-7 cells; its DC50 values against N-Myc are 179 nM in SK-N-BE (2) cells and 229 nM in Kelly cells, respectively. HLB-0532259 induces apoptosis (apoptosis) in MYCN-amplified neuroblastoma cells and inhibits tumor growth in mouse xenograft models. HLB-0532259 can be used for the research of neuroblastoma.
(Pink: Aurora A and N-Myc ligand (HY-168440); Blue: Cereblon ligand (HY-41547); Black: linker (HY-W007957)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 98.30%
- CAS No.: 2566733-45-5
- Formule: C40H44N8O7
- Masse moléculaire:748.83
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
In Vitro
HLB-0532259 binds potently and selectively to recombinant Aurora-A with a Kd value of 6.3 nM, and exhibits only extremely low off-target binding activity in a broad-spectrum profiling panel against various other kinases[1].
HLB-0532259 binds to the recombinant Aurora-A/N-Myc complex with a Kd value of 19.5 nM, which confirms that it does not disrupt the Aurora-A/N-Myc interaction[1].
HLB-0532259 (0.1-0.4 μM; 24 h) upregulates the transcription of AURKA in SK-N-BE (2) and IMR-32 neuroblastoma cells without altering MYCN mRNA levels, which confirms that the reduction of N-Myc occurs at the post-transcriptional level[1].
HLB-0532259 (0-2 μM; 2-5 h) potently and selectively degrades Aurora-A in MCF-7 breast cancer cells via a mechanism dependent on the ubiquitin-proteasome system and requiring simultaneous binding to Aurora-A and CRBN, with a DC50 of 20.2 nM and a Dmax of 94%[1].
HLB-0532259 (0-1.0 μM; 0.5-24 h) simultaneously induces the degradation of Aurora-A and N-Myc in MYCN-amplified SK-N-BE (2), Kelly and IMR-32 neuroblastoma cells, with DC50,app values of N-Myc being 179 nM in SK-N-BE (2) cells and 229 nM in Kelly cells[1].
HLB-0532259 (0-1000 nM; 4-24 h) upregulates the tumor suppressor genes p53 and p21Cip1, downregulates the oncogenes Cyclin Ds, and additionally induces the degradation of Aurora-A and N-Myc in TP53 wild-type IMR-32 neuroblastoma cells in vitro[1].
HLB-0532259 (72-120 h) potently reduces the viability of MYCN-amplified IMR-32, SK-N-BE (2) and Kelly neuroblastoma cells, with IC50 values of 20.1 nM, 71.6 nM and 131 nM, respectively, while exerts much weaker effects on MYCN-non-amplified SK-N-AS cells[1].
HLB-0532259 (0-1000 nM; 24 h) induces apoptosis in TP53 wild-type IMR-32 neuroblastoma cells at concentrations as low as 40 nM, which is confirmed by cleaved PARP-1 and Caspase-3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MYCN-amplified SK-N-BE(2) and IMR-32 neuroblastoma cells
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Concentration:0.1 and 0.4 μM
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Incubation Time:24 hours
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Result:Significantly upregulated AURKA mRNA levels in SK-N-BE(2) and IMR-32 cells.
Had no significant effect on MYCN mRNA levels in either cell line.
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Cell Line:TP53-wildtype IMR-32 neuroblastoma cells
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Concentration:0, 40, 200 and 1000 nM
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Incubation Time:4 hours; 24 hours
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Result:Stabilized p53 protein levels and upregulated p21Cip1 levels.
Downregulated Cyclin D1 and D3 levels, alongside reducing Aurora-A and N-Myc levels.
Exhibited more potent effects than inactive analogue 5, which only inhibited Aurora-A kinase activity without inducing degradation.
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Cell Line:TP53-wildtype IMR-32 neuroblastoma cells
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Concentration:0, 12, 37, 111, 333 and 1000 nM
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Incubation Time:24 hours
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Result:Induced cleavage of PARP-1 and Caspase-3, markers of apoptosis, at concentrations as low as 40 nM.
Showed significantly higher activity in inducing apoptosis compared to inactive analogue 5.
Parmacokinetics
| Species | Dose | Route | Cmax | T1/2 | AUC0-∞ | MRT |
|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 169 ng/mL | 14.5 h | 1993 ng·h/mL | 16.1 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (8-week-old female; subcutaneously inoculated with 5 × 106 MYCN-amplified SK-N-BE(2) cells)[1]
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Dosage:2 mg/kg
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Administration:i.p.; every 2 days; up to 21 days; i.p.; every 3 days; up to 21 days
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Result:Reduced mean tumor volume to 124.9 mm3 9 days post-enrollment when dosed every 2 days.
Reduced mean tumor volume to 50.8 mm3 9 days post-enrollment when dosed every 3 days.
Significantly delayed tumor growth relative to vehicle-treated controls (mean tumor volume 374.4 mm3) for both dosing schedules.
Chemical Information
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CAS No. 2566733-45-5
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Appearance Solid
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Masse moléculaire 748.83
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Formule C40H44N8O7
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Color Off-white to yellow
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SMILES
O=C(N(C)C)C(N1C2CCCC2)=CC3=C1N=C(NC4=CC=C(C(NCCCCCCOC5=C(C(N(C6CCC(NC6=O)=O)C7=O)=O)C7=CC=C5)=O)C=C4)N=C3
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (133.54 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (276 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3354 mL | 6.6771 mL | 13.3542 mL | 33.3854 mL |
| 5 mM | 0.2671 mL | 1.3354 mL | 2.6708 mL | 6.6771 mL | |
| 10 mM | 0.1335 mL | 0.6677 mL | 1.3354 mL | 3.3385 mL | |
| 15 mM | 0.0890 mL | 0.4451 mL | 0.8903 mL | 2.2257 mL | |
| 20 mM | 0.0668 mL | 0.3339 mL | 0.6677 mL | 1.6693 mL | |
| 25 mM | 0.0534 mL | 0.2671 mL | 0.5342 mL | 1.3354 mL | |
| 30 mM | 0.0445 mL | 0.2226 mL | 0.4451 mL | 1.1128 mL | |
| 40 mM | 0.0334 mL | 0.1669 mL | 0.3339 mL | 0.8346 mL | |
| 50 mM | 0.0267 mL | 0.1335 mL | 0.2671 mL | 0.6677 mL | |
| 60 mM | 0.0223 mL | 0.1113 mL | 0.2226 mL | 0.5564 mL | |
| 80 mM | 0.0167 mL | 0.0835 mL | 0.1669 mL | 0.4173 mL | |
| 100 mM | 0.0134 mL | 0.0668 mL | 0.1335 mL | 0.3339 mL |
HLB-0532259 Related Classifications
HY-168439 Related Classifications
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