JP-11646
Based on 1 Customer Validation
JP-11646 is a pan-PIM inhibitor with increased potency against PIM2 (IC50 = 0.5 nM). JP11646 is freely reversible and ATP non-competitive. JP-11646 results in a decrease of PIM1, 2, and 3 mRNA. JP-11646 can effectively inhibit cell viability in small cell lung cancer (SCLC) and large cell neuroendocrine carcinomas of the lung (LCNEC). JP-11646 can cause a decrease in p-4EBP-1 protein, increasing the cleavage of caspases while decreasing caspase-3. JP-11646 induces apoptosis or necroptosis in cells. JP-11646 leads to reductions in MYC paralogs. JP-11646 can be used for the study of SCLC, LCNEC, human acute leukemia (AML), multiple myeloma (MM), and triple-negative breast cancer (TNBC).
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- Pureté : 98.74%
- CAS No.: 1902983-63-4
- Formule: C25H25N5O2S
- Masse moléculaire:459.56
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Stockage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
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NF-κB |
Caspase 3 |
PIM2 0.5 nM (IC50) |
In Vitro
JP11646 (0.005 to 10 μM, 72 h) inhibits the proliferation of all tested cancer cell lines in a concentration-dependent manner, including head and neck cancer FaDu, ovarian cancer SK-OV-3, breast cancer MDA-MB-231 and BT549, prostate cancer PC-3, liver cancer HepG2, PDAC MIAPaCa-2 and PANC1, colorectal cancer DLD-1 and HT29, and NSCLC H1650, H661, H460 and A549 cell lines[3].
JP11646 (100-200 nM, 24 h) selectively downregulates the protein expression level of PIM2, but has no effect on PIM1 and PIM3, and induces the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells[3].
JP11646 (100-200 nM, 48 h) significantly increases the apoptosis rate of MDA-MB-231 and BT549 cells[3].
JP11646 (20-200 nM, 0-24 h) gradually reduces the levels of p4EBP1 (S65) and pBAD (S112) in MM1.S and U266 cells over time, as do the total levels of these proteins. Furthermore, the levels of the potent phosphorylates form of the anti-apoptotic factor MCL1 (Ser159/Thr163) decrease in a dose-dependent manner[4].
JP11646 (0-1 μM, 72 h) shows the strongest antiproliferative effect against the MF characteristic cell line MM1.S (GI50 = 5 nM)[4].
JP11646 (20-200 nM, 24 h) can reverse (recombinant IL-6) rIL-6-induced PIM2 upregulation in MM1.S and U266 cells, while IL-6 does not affect PIM2 mRNA levels[4].
JP11646 (10-20 nM, 48 h) reverses the chemoprotective effect mediated by CD28 activation or DC co-culture; CTLA4-Ig enhances the cytotoxicity of JP11646[4].
JP11646 (20-200 nM, 0-24 h) dose- and time-dependently inhibits CD28-induced NF-κB activity in MM1.S and RPMI8226 cells[4].
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:MDA-MB-231 cells, BT549 cells
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Concentration:100 nM, 200 nM
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Incubation Time:24 h
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Result:Downregulated the protein expression level of PIM2, but had no effect on PIM1 and PIM3, and induced the expression of the apoptosis marker cleaved PARP in MDA-MB-231 and BT549 cells.
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Cell Line:MDA-MB-231 cells, BT549 cells
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Concentration:100 nM, 200 nM
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Incubation Time:48 h
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Result:Significantly increased the apoptosis rate of MDA-MB-231 and BT549 cells.
In Vivo
JP11646 (10-15 mg/kg, i.p., 2 or 3 times a week for 48 days) demonstrates potent dose-dependent antitumor activity in a mice model of multiple myeloma xenograft and significantly prolongs the median survival of tumor-bearing mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Cell suspensions (1×106 of MDA‑MB‑231, 3×106 of MIAPaCa‑2, 2×106 of PANC‑1, 5×106 of HepG2, 5×106 of A549, 5×106 of HT29 and 5×106 of H1650) in a mixture of 50 µl PBS and 50 µl Matrigel were injected subcutaneously into the CB17 SCID mice (female, 6‑8 weeks‑old, weighing 18‑22 g) flanks, or in the case of MDA‑MB‑231 cells, into the abdomen mammary fat pads[3].
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Dosage:15 mg/kg
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Administration:I.p., twice every week (MDA‑MB‑231, 24 days; HepG2, 23 days; MIAPaCa‑2, 29 days; PANC‑1, 40 days; A549, 29 days; H1650, 18 days; HT29, 12 days)
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Result:Demonstrated significant tumor growth inhibition in five models: MDA-MB-231 (breast cancer), HepG2 (liver cancer), MIAPaCa-2 (pancreatic cancer), A549 (lung cancer), and H1650 (lung cancer).
Did not show significant efficacy in two models (PANC-1 pancreatic cancer and HT29 colorectal cancer).
No mice experienced weight loss exceeding 20% or other detectable serious side effects.
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Animal Model:SCID/SCIDCBIgh.lblcrTac.Prkdcscid/Ros mice < 5 weeks of age were irradiated at 300 rads using a Mark II Cesium irradiator 24 hours before injecting them with MM1.S cells (5×106) subcutaneously under the skin on the left ventral flank[4].
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Dosage:10 mg/kg, 15 mg/kg
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Administration:I.p., 2 or 3 times a week for 48 days
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Result:The relative tumor volume in the 10 mg/kg and 15 mg/kg groups was reduced to 49% and 89% of that in the control group, respectively.
The 15 mg/kg group showed a tumor reduction of over 91%.
The median survival in the 10 mg/kg group was prolonged to 27 days.
The median survival in the 15 mg/kg group was significantly prolonged to 48 days.
During the two-week observation period after treatment cessation in the 15 mg/kg group, two of the three surviving mice did not show tumor regeneration.
Chemical Information
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CAS No. 1902983-63-4
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Appearance Solid
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Masse moléculaire 459.56
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Formule C25H25N5O2S
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Color Light yellow to yellow
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SMILES
O=C1NC(/C(S1)=C/C2=CC=NC(N[C@H]3CC[C@@H](CC3)NCC4=CC=CC5=C4C=CC=C5)=N2)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (217.60 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 (protect from light). 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 (protect from light). 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.44 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.44 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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 (protect from light)
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.
Protocole
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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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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CCK-8/WST-8 Cell Proliferation Assay
The CCK-8/WST-8 assay is based on the reduction of the water-soluble tetrazolium salt WST-8 to a water-soluble formazan product by cellular dehydrogenases in metabolically active cells, where the generated formazan amount is proportional to the number of living cells and is quantified by measuring absorbance in the visible range, providing a colorimetric readout for cell viability and proliferation assessment. This class of tetrazolium-based assays improves upon earlier MTT-based systems by producing a water-soluble formazan, eliminating the need for organic solubilization steps and enabling direct spectrophotometric measurement in culture medium.
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MTT Cell Proliferation Assay
The MTT assay is a colorimetric endpoint assay for estimating viable cell number, cell growth, cytotoxicity, or cell activation in cultured mammalian cells. Living cells reduce the yellow tetrazolium salt MTT into purple/blue formazan, while dead cells do not generate the same signal; the resulting color can be quantified with a multiwell spectrophotometer. MTT reduction is commonly interpreted as a readout of metabolic activity that often correlates with viable cell number, but it should not be treated as a direct cell-counting method unless the assay is optimized for the cell type and experimental condition. Studies show that MTT reduction can involve mitochondrial and non-mitochondrial reducing systems, and formazan may accumulate in intracellular lipid droplets rather than simply marking mitochondria.
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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.
Pureté et documentation
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Fiche technique (285 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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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 (protect from light). 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 |
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| DMSO | 1 mM | 2.1760 mL | 10.8800 mL | 21.7599 mL | 54.3999 mL |
| 5 mM | 0.4352 mL | 2.1760 mL | 4.3520 mL | 10.8800 mL | |
| 10 mM | 0.2176 mL | 1.0880 mL | 2.1760 mL | 5.4400 mL | |
| 15 mM | 0.1451 mL | 0.7253 mL | 1.4507 mL | 3.6267 mL | |
| 20 mM | 0.1088 mL | 0.5440 mL | 1.0880 mL | 2.7200 mL | |
| 25 mM | 0.0870 mL | 0.4352 mL | 0.8704 mL | 2.1760 mL | |
| 30 mM | 0.0725 mL | 0.3627 mL | 0.7253 mL | 1.8133 mL | |
| 40 mM | 0.0544 mL | 0.2720 mL | 0.5440 mL | 1.3600 mL | |
| 50 mM | 0.0435 mL | 0.2176 mL | 0.4352 mL | 1.0880 mL | |
| 60 mM | 0.0363 mL | 0.1813 mL | 0.3627 mL | 0.9067 mL | |
| 80 mM | 0.0272 mL | 0.1360 mL | 0.2720 mL | 0.6800 mL | |
| 100 mM | 0.0218 mL | 0.1088 mL | 0.2176 mL | 0.5440 mL |
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