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)).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit : 98.30%
- CAS. Nr.: 2566733-45-5
- Formel: C40H44N8O7
- Molecular Weight:748.83
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Speicherung: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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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
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Biologische Aktivität
Beschreibung
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. Further protocols information, click here.
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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 |
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| 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. Nr. 2566733-45-5
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Appearance Solid
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Molecular Weight 748.83
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Formel 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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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
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.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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.
Protokoll
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Reinheit & Dokumentation
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Data Sheet (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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Handling Instructions (2659 KB)
Verweise
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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