JWZ-8-103
Based on 1 Customer Validation
JWZ-8-103 is an orally active analog of PRLX-93936 (HY-119264) and a molecular glue targeting TRIM21. JWZ-8-103 increases the thermal stability of TRIM21. JWZ-8-103 promotes rapid and efficient interaction between TRIM21 and NUP98 (the apparent EC50 for ternary complex formation with the PRYSPRY domain of TRIM21 and the APD domain of NUP98 is approximately 20 μM), induces extensive ubiquitination and proteasomal degradation of numerous adjacent nucleoporins (NUPs, and thereby triggers cellular apoptosis. JWZ-8-103 can be used for the research of pancreatic cancer.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 98.04%
- CAS 番号: 3110272-60-8
- 分子式: C21H22ClFN4O2
- 分子量:416.88
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保管条件:
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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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
apparent EC50 = ∼20 μM (ternary complex formation between TRIM21 PRYSPRY and NUP98 APD in the presence of JWZ-8-103)[1]
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| PANC-1 | IC50 |
9.5 nmol/L
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Reduction of cell viability against wild-type PANC-1 human pancreatic cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
Reduction of cell viability against wild-type PANC-1 human pancreatic cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
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40891634 |
| PANC-1 | IC50 |
>10 μmol/L
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Reduction of cell viability against TRIM21 knockout PANC-1 human pancreatic cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
Reduction of cell viability against TRIM21 knockout PANC-1 human pancreatic cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
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40891634 |
| NCI-H661 | IC50 |
<10 nmol/L
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Reduction of cell viability against TRIM21-overexpressing H661 human lung cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
Reduction of cell viability against TRIM21-overexpressing H661 human lung cancer cells assessed via CellTiter-Glo luminescent assay after 72 h incubation.
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40891634 |
体外実験
JWZ-8-103 (10-100 μM; 1 h) enhances the thermal stability of TRIM21 protein in PANC-1 cell lysates[1].
JWZ-8-103 (10 μM; 1 h) functions to promote the interaction between TRIM21 and NUP98 in lysates of PANC-1 cells with TRIM21 knockout and Flag-TRIM21 re-expression[1].
JWZ-8-103 (100 nM; 6 h) broadly induces TRIM21-dependent nucleoporin degradation in wild-type PANC-1 cells[1].
JWZ-8-103 (up to 10 μM; monitored continuously for up to 2 h) rapidly induces the proximity interaction between TRIM21 and NUP98 in HEK293T cells, and confirms that there is no direct interaction between TRIM21 and MCL1[1].
JWZ-8-103 (20 μM; for approximately 1 h) promotes the direct binding between TRIM21 PRYSPRY and GST-NUP98 APD in purified proteins in vitro[1].
JWZ-8-103 (15-20 nM; 21-22 days) exhibits significant cytotoxicity in PANC-1 cells, and this effect depends on specific amino acid binding sites on TRIM21[1].
JWZ-8-103 (0.5 μM; 6 h) blocks mRNA nuclear export and causes the retention of MCL1 and c-MYC transcripts in the nucleus in PANC-1 cells[1].
JWZ-8-10 (2-24 h) exhibits significant differential toxicity in PANC-1 and non-malignant RPE1-hTERT cells: transient treatment induces irreversible cell death in PANC-1 cells, while RPE1-hTERT cells survive and recover[1].
JWZ-8-103 (72 h) exhibits potent anti-proliferative activity in wild-type PANC-1 cells (IC50 = 9.5 nM) and TRIM21-overexpressing H661 cells (IC50 < 10 nM), but loses this activity in TRIM21-knockout cells[1].
JWZ-8-103 (for 5 days) exhibits potent activity in inhibiting cell viability and degrading NUP98, GLE1 and MCL1 proteins in TRIM21-highly expressed pancreaticobiliary organoids (HCMI PDOs, including PDM-30, PDM-31, PDM-39, PDM-166), but shows no efficacy in low-expression models[1].
JWZ-8-103 (0.1-5 μM; 6 h) exhibits activity that induces substantial degradation of nuclear pore complex proteins and short-lived anti-apoptotic proteins in PANC-1, KP3, Hs766T, and MIA PaCa-2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:PANC-1, KP3, Hs766T, MIA PaCa-2 cells
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Concentration:6 h, 24 h
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Incubation Time:0.1, 0.5, 1, 5 μM
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Result:Induced a marked decrease in downstream nuclear pore target proteins and short-lived transcript-derived proteins, accompanied by observed cleavage/activation of Caspase-3, Caspase-7, and PARP at 24 hours.
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Cell Line:PANC-1 cells
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Concentration:6 h
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Incubation Time:0.5 μM
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Result:Resulted in severe abnormal nuclear retention of mRNAs encoding key pro-survival factors (MCL1 and c-MYC), demonstrating a clear blockade of nucleocytoplasmic transport.
Parmacokinetics
体内実験
JWZ-8-103 (15 mg/kg; i.p.; once daily; for 21 consecutive days) induces near-complete tumor regression in HS766T pancreatic cancer xenograft models with good tolerability[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (female, 6 weeks old, subcutaneous xenograft of PANC-1 human pancreatic cancer cells)[1]
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Dosage:15 mg/kg; 50 mg/kg
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Administration:i.p.; once daily; 21 days
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Result:Reduced mean tumor volume to 71 mm3 (87.0% reduction vs. vehicle) at 15 mg/kg.
Reduced mean tumor volume to 77 mm3 (85.8% reduction vs. vehicle) at 50 mg/kg.
Achieved tumor regression relative to baseline at both doses.
Depleted nuclear pore complex proteins (NUPs) in tumor tissue collected 2 hours after the second daily dose.
Was well tolerated with no signs of toxicity.
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Animal Model:NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (female, 6 weeks old, subcutaneous xenograft of HS766T human pancreatic cancer cells)[1]
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Dosage:15 mg/kg
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Administration:i.p.; once daily; 21 days
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Result:Reduced mean tumor volume to 0.5 mm3 (>99% reduction vs. vehicle), representing near-complete tumor regression.
Was well tolerated with no evidence of body weight loss.
化学情報
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CAS 番号 3110272-60-8
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性状 Solid
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分子量 416.88
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分子式 C21H22ClFN4O2
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Color White to off-white
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SMILES
CCOC1=CC(Cl)=CC=C1N2C(C3=CC(F)=CC=C3N=C2CN4CCNCC4)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (239.88 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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
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 (6.00 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 (6.00 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.
純度とドキュメンテーション
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データシート (281 KB)
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SDS (252 KB)
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取扱説明書 (2659 KB)
参考文献
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3988 mL | 11.9939 mL | 23.9877 mL | 59.9693 mL |
| 5 mM | 0.4798 mL | 2.3988 mL | 4.7975 mL | 11.9939 mL | |
| 10 mM | 0.2399 mL | 1.1994 mL | 2.3988 mL | 5.9969 mL | |
| 15 mM | 0.1599 mL | 0.7996 mL | 1.5992 mL | 3.9980 mL | |
| 20 mM | 0.1199 mL | 0.5997 mL | 1.1994 mL | 2.9985 mL | |
| 25 mM | 0.0960 mL | 0.4798 mL | 0.9595 mL | 2.3988 mL | |
| 30 mM | 0.0800 mL | 0.3998 mL | 0.7996 mL | 1.9990 mL | |
| 40 mM | 0.0600 mL | 0.2998 mL | 0.5997 mL | 1.4992 mL | |
| 50 mM | 0.0480 mL | 0.2399 mL | 0.4798 mL | 1.1994 mL | |
| 60 mM | 0.0400 mL | 0.1999 mL | 0.3998 mL | 0.9995 mL | |
| 80 mM | 0.0300 mL | 0.1499 mL | 0.2998 mL | 0.7496 mL | |
| 100 mM | 0.0240 mL | 0.1199 mL | 0.2399 mL | 0.5997 mL |
JWZ-8-103 関連分類
HY-180654 関連分類
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