SJ988497
Based on 1 Customer Validation
SJ988497 is a PROTAC degrader targeting JAK2. SJ988497 induces the proteasomal degradation of CRBN-mediated JAK2, JAK1, JAK3, GSPT1, and IKZF1, and functions as a CRBN neosubstrate for GSPT1. SJ988497 retains binding affinity for the kinase domain of JAK2. SJ988497 can be used in studies related to cancers such as crlf2-rearranged acute lymphoblastic leukemia.
(Pink: JAK2 ligand (HY-184994); Blue: Cereblon ligand (HY-41547); Black: linker).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity: 99.03%
- CAS No.: 2595365-41-4
- 화학식: C36H36N10O5
- 분자량:688.74
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
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JAK2 |
eRF3a/GSPT1 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MHH-CALL-2 | EC50 |
2.2 nM
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Cytotoxicity against B-progenitor ALL MHH-CALL-2 cells incubated for 72 hrs by resazurin assay.
Cytotoxicity against B-progenitor ALL MHH-CALL-2 cells incubated for 72 hrs by resazurin assay.
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34110416 |
| NALM-6 | EC50 |
13.3 nM
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Cytotoxicity against B-progenitor ALL NALM-6 cells incubated for 72 hrs by resazurin assay.
Cytotoxicity against B-progenitor ALL NALM-6 cells incubated for 72 hrs by resazurin assay.
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34110416 |
| 697 | EC50 |
4.2 nM
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Cytotoxicity against B-progenitor ALL 697 cells incubated for 72 hrs by resazurin assay.
Cytotoxicity against B-progenitor ALL 697 cells incubated for 72 hrs by resazurin assay.
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34110416 |
| CD34+ cells | EC50 |
1.3 nM
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Cytotoxicity against normal human hCD34+ cord blood cells incubated for 72 hrs by resazurin assay.
Cytotoxicity against normal human hCD34+ cord blood cells incubated for 72 hrs by resazurin assay.
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34110416 |
In Vitro
SJ988497 (72 h) potently reduces viability of multiple acute lymphoblastic leukemia cell lines in a CRBN-dependent manner, with an EC50 of 0.4 nM in CRLF2-rearranged MHH-CALL-4 parental ALL cells[1].
SJ988497 (compound 7) mediates target protein degradation in MHH-CALL-4 human acute lymphoblastic leukemia cells[2].
SJ988497 degrades its target protein, suppresses JAK-STAT pathway signaling, and induces cytotoxicity in MHH-CALL-4 human acute lymphoblastic leukemia cells[2].
SJ988497 produces cytotoxicity and mediates target protein degradation in ex vivo cultured MHH-CALL-4 human acute lymphoblastic leukemia cells[2].
SJ988497 demonstrates high cellular permeability in the Caco-2 assay, consistent with its optimized low molecular weight and reduced polar surface area that improves cellular uptake[1].
SJ988497 maintains high binding affinity for the JAK2 target with a distribution coefficient of 0.3 nM, comparable to the affinity of its parent JAK inhibitor scaffold[1].
SJ988497 (1 h) achieves equivalent JAK signaling inhibition levels as the parent JAK inhibitor Ruxolitinib (HY-50856) in TSLP-stimulated MHH-CALL-4 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:B-progenitor ALL cell lines (MHH-CALL-4 parental, MHH-CALL-4 CRBN-KD, KOPN49, MHH-CALL-2, KOPN75, NALM-6, 697) and normal human hCD34+ cord blood cells
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Concentration:1.5 μM (baricitinib cotreatment); 30 μM (cereblon-binding immunomodulatory imide drug cotreatment)
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Incubation Time:72 h
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Result:Exhibited an EC50 of 0.4 nM in MHH-CALL-4 parental cells, which increased to 3456.2 nM in CRBN-knockdown MHH-CALL-4 cells.
Recorded EC50 values of 1.1 nM in KOPN49 cells, 2.2 nM in MHH-CALL-2 cells, 1.0 nM in KOPN75 cells, 13.3 nM in NALM-6 cells, 4.2 nM in 697 cells, and 1.3 nM in normal hCD34+ cells.
Showed no reduced activity with 1.5 μM baricitinib cotreatment.
Had completely abolished cytotoxic activity with 30 μM cereblon-binding immunomodulatory imide drug cotreatment, with EC50 >57 nM.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, female, 8 to 12 weeks old[1]
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Dosage:30 mg/kg (efficacy); 10 mg/kg (pharmacodynamic); 30 mg/kg (pharmacodynamic); 100 mg/kg (pharmacodynamic)
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Administration:i.p.; once daily; 28 days (efficacy); i.p.; twice daily (pharmacodynamic)
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Result:Induced dose-dependent inhibition of JAK2 and STAT5 phosphorylation, as well as dose-dependent degradation of JAK family proteins and GSPT1, with near-maximal effects observed at the 30 mg/kg dose.
Maintained sustained in vivo plasma exposure exceeding the cellular 50% effective concentration for at least 24 hours after intraperitoneal dosing.
Produced a substantial reduction of leukemia burden measured in bone marrow, blood, spleen, and total body bioluminescent imaging following once-daily 30 mg/kg i.p. administration for 28 days.
Showed no observed weight loss or perturbation of blood cell counts over the 28-day dosing period.
Chemical Information
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CAS No. 2595365-41-4
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Appearance Solid
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분자량 688.74
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화학식 C36H36N10O5
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Color Light yellow to yellow
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SMILES
CCCN1C=C(C=N1)C2=C3C=CNC3=NC(NC4=CC=C(C=C4)C(NCCCCNC5=C6C(N(C(C6=CC=C5)=O)C7CCC(NC7=O)=O)=O)=O)=N2
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 33.33 mg/mL (48.39 mM; ultrasonic and warming and heat to 80°C; 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (3.63 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
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.
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.
순도&문서
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Data Sheet (286 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)
References
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 | 1.4519 mL | 7.2596 mL | 14.5193 mL | 36.2982 mL |
| 5 mM | 0.2904 mL | 1.4519 mL | 2.9039 mL | 7.2596 mL | |
| 10 mM | 0.1452 mL | 0.7260 mL | 1.4519 mL | 3.6298 mL | |
| 15 mM | 0.0968 mL | 0.4840 mL | 0.9680 mL | 2.4199 mL | |
| 20 mM | 0.0726 mL | 0.3630 mL | 0.7260 mL | 1.8149 mL | |
| 25 mM | 0.0581 mL | 0.2904 mL | 0.5808 mL | 1.4519 mL | |
| 30 mM | 0.0484 mL | 0.2420 mL | 0.4840 mL | 1.2099 mL | |
| 40 mM | 0.0363 mL | 0.1815 mL | 0.3630 mL | 0.9075 mL |
SJ988497 Related Classifications
HY-151902 Related Classifications
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