JP-163-16
Based on 1 Customer Validation
JP-163-16 is a NF-κB RelA/p65 PROTAC degrader that recruits CRBN. JP-163-16 selectively induces RelA/p65 degradation via the ubiquitin-proteasome pathway, exerts cytotoxicity and induces apoptosis in cancer cells, while showing low toxicity to non-malignant lymphocytes. JP-163-16 can be used for the research of chronic lymphocytic leukemia, triple-negative breast cancer and multiple myeloma.
(Pink: p65 and RelA ligand (HY-174865); Blue: Cereblon ligand (HY-A0003); Black: linker).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit : 99.20%
- CAS. Nr.: 3100147-70-1
- Formel: C42H47N7O8
- Molecular Weight:777.86
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Speicherung:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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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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
IC50 & Target
[1]|
p65 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MEC1 | LC50 |
0.14 μM
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Apoptosis induction in human MEC-1 chronic lymphocytic leukaemia cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
Apoptosis induction in human MEC-1 chronic lymphocytic leukaemia cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
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40443648 |
| RPMI-8226 | LC50 |
0.70 μM
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Apoptosis induction in human RPMI-8226 cereblon-deficient myeloma cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
Apoptosis induction in human RPMI-8226 cereblon-deficient myeloma cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
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40443648 |
| MDA-MB-231 | LC50 |
2.9 μM
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Apoptosis induction in human MDA-MB-231 triple-negative breast cancer cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
Apoptosis induction in human MDA-MB-231 triple-negative breast cancer cells assessed by FITC annexin V and 7-AAD staining followed by flow cytometry after 48 hrs of incubation.
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40443648 |
In Vitro
JP-163-16 (compound 15d) (0.0625-1 μM; 48 h) potently induces apoptosis in MEC-1 chronic lymphocytic leukemia (CLL) cells, with an LC50 of 0.14 μM[1].
JP-163-16 (0.0625-1 μM; 48 h) exerts proapoptotic effects on MEC-1 chronic lymphocytic leukemia (CLL) cells, and this effect is proteasome-dependent[1].
JP-163-16 (0.0625-1 μM; 48 h) induces apoptosis in primary chronic lymphocytic leukemia (CLL) cells with an LC50 of 0.23 μM[1].
JP-163-16 (48 h) exhibits two orders of magnitude lower toxicity toward normal primary B lymphocytes (LD50: 19.1 μM) and T lymphocytes (LD50: 36.4 μM) than toward malignant chronic lymphocytic leukemia (CLL) cells[1].
JP-163-16 (10 nM-1 μM; 48 h) exhibits a five-fold reduction in cytotoxic potency in cereblon-deficient RPMI-8226 myeloma cells, with an LC50 of 0.70 μM, indicating that its activity is dependent on cereblon[1].
JP-163-16 (0.0625-1 μM; 48 h) induces apoptosis in MDA-MB-231 triple-negative breast cancer cells, with an LC50 of 2.9 μM[1].
JP-163-16 (0.0625-1 μM; 48 h) exerts proteasome-dependent proapoptotic effects on MDA-MB-231 triple-negative breast cancer cells[1].
JP-163-16 (10 μM) does not interact significantly with AT-rich DNA[1].
JP-163-16 (0.5-1 μM; 24 h) selectively depletes RelA/p65 expression in MEC-1 chronic lymphocytic leukemia (CLL) cells, with no persistent effect on RelB or cRel[1].
JP-163-16 (0.5-1 μM; 24 h) reduces the expression level of RelA/p65 in triple-negative breast cancer cells MDA-MB-231, and this effect is proteasome-dependent[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:MEC-1 chronic lymphocytic leukaemia cells
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Concentration:0.0625, 0.125, 0.25, 0.5, 1 μM
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Incubation Time:48 h
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Result:Induced dose-dependent apoptosis, with a mean LC50 value of 0.14 μM.
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Cell Line:MEC-1 CLL cells
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Concentration:0.0625, 0.125, 0.25, 0.5, 1 μM
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Incubation Time:48 h
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Result:Showed significantly reduced cytotoxicity when co-treated with proteasome inhibitor MG-132, with an increased mean LC50 value relative to JP-163-16 alone.
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Cell Line:RPMI-8226 cereblon-deficient myeloma cells
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Concentration:10, 100, 1000 nM
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Incubation Time:48 h
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Result:Showed a five-fold reduction in potency, with an LC50 of 0.70 μM (compared to 0.14 μM in MEC-1 cells).
Chemical Information
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CAS. Nr. 3100147-70-1
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Appearance Solid
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Molecular Weight 777.86
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Formel C42H47N7O8
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Color White to off-white
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SMILES
O=C(NC1=CC=C(NC(CCCOC2=C(OC)C=C3C(N=C[C@@](CCC4)([H])N4C3=O)=C2)=O)C=C1)CCCCCNC5=CC=CC6=C5CN(C(CC7)C(NC7=O)=O)C6=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : ≥ 100 mg/mL (128.56 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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 (stored under nitrogen). 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 (stored under nitrogen). 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.21 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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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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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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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Reinheit & Dokumentation
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Data Sheet (282 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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 (stored under nitrogen). 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 | 1.2856 mL | 6.4279 mL | 12.8558 mL | 32.1395 mL |
| 5 mM | 0.2571 mL | 1.2856 mL | 2.5712 mL | 6.4279 mL | |
| 10 mM | 0.1286 mL | 0.6428 mL | 1.2856 mL | 3.2139 mL | |
| 15 mM | 0.0857 mL | 0.4285 mL | 0.8571 mL | 2.1426 mL | |
| 20 mM | 0.0643 mL | 0.3214 mL | 0.6428 mL | 1.6070 mL | |
| 25 mM | 0.0514 mL | 0.2571 mL | 0.5142 mL | 1.2856 mL | |
| 30 mM | 0.0429 mL | 0.2143 mL | 0.4285 mL | 1.0713 mL | |
| 40 mM | 0.0321 mL | 0.1607 mL | 0.3214 mL | 0.8035 mL | |
| 50 mM | 0.0257 mL | 0.1286 mL | 0.2571 mL | 0.6428 mL | |
| 60 mM | 0.0214 mL | 0.1071 mL | 0.2143 mL | 0.5357 mL | |
| 80 mM | 0.0161 mL | 0.0803 mL | 0.1607 mL | 0.4017 mL | |
| 100 mM | 0.0129 mL | 0.0643 mL | 0.1286 mL | 0.3214 mL |
JP-163-16 Related Classifications
HY-174864 Related Classifications
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